PubAnnotation

Id	Subject	Object	Predicate	Lexical cue
T1	0-935	Epistemic_statement	denotes	DVP01 "Inactivated mycobacteria bead preparation" method for identification of mycobacteria by MALDI-TOF MS DVP02 MALDI-TOF MS for functional detection of ß-lactam resistance of positive blood cultures DVP03 Molecular typing of Stenotrophomonas maltophilia from patients with cystic fibrosis by repetitive sequence-based PCR DVP04 Photochemical inactivation allows papid diagnostics of Alpha- and Poxviruses DVP05 Rapid detection and molecular differentiation of toxigenic Corynebacterium diphtheriae and Corynebacterium ulcerans strains by LightCycler PCR DVP06 Use of recombinant proteins for optimized serodiagnosis of M. pneumoniae infections DVP07 MALDI-TOF-MS analysis of bacteria difficult to identify by standard procedures DVP08 Carbapenemase detection by phenotypic methods DVP09 Direct identification of uropathogens by MALDI-TOF-MS and interfering factors DVP10 Comparison of different methods for the isolation of tick DNA
T2	946-1131	Epistemic_statement	denotes	Introduction: Next to the clinical important Mycobacterium tuberculosis complex (MTC) Nontuberculosis mycobacteria (NTM) are pathogens especially in immunocompromised and senior people.
T3	5911-6053	Epistemic_statement	denotes	Therefore, only the decrease of the molecular peak of Ertapenem can be employed as indicator for resistance against carbapenems at the moment.
T4	6054-6240	Epistemic_statement	denotes	Additional peaks appear in the spectra of the carbapenemase positive strains but these do not directly correspond to the hydrolyzed form of Ertapenem and have not been identified so far.
T5	7643-7772	Epistemic_statement	denotes	A small proportion of isolates were clonally related (12%), suggesting either cross-transmissions or a common source of exposure.
T6	8003-8289	Epistemic_statement	denotes	The objective of this study was to determine whether photochemical inactivation of viruses could be accomplished with high efficiency while preserving the molecular integrity of viral targets allowing subsequent diagnostic tests to be performed at a lower level of containment and cost.
T7	8993-9277	Epistemic_statement	denotes	The presented data could assist in developing methods to inactivate in the field environmental and forensic samples suspected of contamination with high virulence virus, thus limiting the need for costly security and safety operations after an accidental or intentional viral release.
T8	9786-9975	Epistemic_statement	denotes	Since the respective tox genes of C. diphtheriae and C. ulcerans differ in both DNA and amino acid sequence from each other, both tox genes should be covered by novel real-time PCR methods.
T9	10263-10539	Epistemic_statement	denotes	Background: Detection of Enterobacteriaceae carrying carbapenemases is challenging since the MIC can be in the susceptible range and because differentiation between carbapenem resistance due to carbapenemases or other mechanisms is not possible by routine susceptible testing.
T10	12027-12125	Epistemic_statement	denotes	Conclusions: In contrast to recommendations by CLSI the MHT should also be performed for imipenem.
T11	12126-12225	Epistemic_statement	denotes	Despite a lower specifity the importance of carbapenemase detection justifies a higher sensitivity.
T12	12226-12342	Epistemic_statement	denotes	Caution should be used in choosing the test media since huge differences in metallobetalactamase detection are seen.
T13	14024-14191	Epistemic_statement	denotes	These proteins are produced naturally in the body and cannot be removed simply by washing the filter residue because they closely interact with the bacterial membrane.
T14	14278-14385	Epistemic_statement	denotes	In ticks different pathogens can be found that may cause serious infections in humans and domestic animals.
T15	14628-14801	Epistemic_statement	denotes	Since the question regarding optimal DNA extraction from ticks is only poorly addressed so far, the present study compared different methods for isolation of DNA from ticks.
T16	17054-17211	Epistemic_statement	denotes	As minimal inhibitory concentration (MIC) of these strains can be increased but below the standard CLSI-breakpoints, further confirmatory tests are required.
T17	18320-18371	Epistemic_statement	denotes	By PCR 26 ESBL-positive E. coli could be confirmed.
T18	18898-18974	Epistemic_statement	denotes	However, use of disk diffusion tests is often more staff-and time-intensive.
T19	18975-19100	Epistemic_statement	denotes	Background: Enterobacteriaceae resistant to carbapenems are a growing problem in an increasing number of countries worldwide.
T20	19101-19230	Epistemic_statement	denotes	In Germany, carbapenemase resistance is still rare, but appears to be rising, and several hospital outbreaks have been described.
T21	20209-20360	Epistemic_statement	denotes	Random PCR (RAPD) was attempted to prove clonal origin of the isolates, yet, in case of these K. pneumoniae isolates the method was not discriminative.
T22	20361-20689	Epistemic_statement	denotes	As an alternative for rapid typing, MALDI-TOF spectra of isolates were compared yielding an excellent spectrum identity between outbreak strains and a good discrimination towards other unrelated isolates, yet, automated calculation of the dendrogram by the biotyper software was not applicable for intra-species differentiation.
T23	20849-20989	Epistemic_statement	denotes	RAPD), the diagnostic use of MALDI-TOF spectra may be helpful for preliminary epidemiologic analysis of clinical outbreaks within few hours.
T24	20990-21118	Epistemic_statement	denotes	The values and limitations of the method need to be further validated for different microorganisms by a standard procedure (e.g.
T25	21119-21268	Epistemic_statement	denotes	PFGE, MLST), yet, ease of applicability and low running costs make mass spectra analysis a promising tool for first line clinical outbreaks analysis.
T26	24572-24786	Epistemic_statement	denotes	We examined whether the analysis of bacterial protein patterns by MALDI-TOF-MS (Matrix-assisted laser desorption/ionization time of flight mass spectrometry) results in an unequivocal identification in those cases.
T27	24787-25109	Epistemic_statement	denotes	Methods: Isolates obtained from tissues and fluids of patients in the clinical routine which could not be unambiguously identified by API ® or VITEK ® or by gas chromatography, respectively, were analyzed by MALDI-TOF-MS. A small number of bacterial cells from the culture plate was directly deposited onto a sample plate.
T28	25483-25668	Epistemic_statement	denotes	Results: By using MALDI-TOF-MS analysis we could identify nearly 80 % of all isolates which previously had not given a clear result when standard identification procedures were applied.
T29	25669-25776	Epistemic_statement	denotes	In most cases the bacteria could be identified at the species level, in some cases only at the genus level.
T30	27296-27564	Epistemic_statement	denotes	Although, studies dealing with cost effectiveness of PCR in the management of CDAD patients are sparse, the BD GenOhm Cdiff assay (PCR) has greater analytical sensitivity than a conventional toxin ELISA maintaining comparable specificity in samples from CADA patients.
T31	27565-28021	Epistemic_statement	denotes	A. Halfmann* 1 , U. Geipel 1 , L. von Müller 1 , M. Herrmann 1 1 University Hospital of Saarland, Institute for Medical Microbiology and Hygiene, Homburg, Deutschland Background: Universal screening for methicillin-resistant Staphylococcus aureus (MRSA) is a valuable tool to estimate MRSA prevalence, yet, for a single institution, the laboratory challenges of a large campaign requiring quality-assured handling and processing of samples can be enormous.
T32	29380-29634	Epistemic_statement	denotes	Subsequently, several modifications on the WASP specimen processing protocol (various vortexing times, quantities of medium plated or streaking patterns) were carried out with support of the readily available WASP technical team both on-line and on-site.
T33	30902-31023	Epistemic_statement	denotes	Most people become infected with EBV at an early age, which is often asymptomatic but may cause infectious mononucleosis.
T34	31111-31265	Epistemic_statement	denotes	Although the symptoms of infectious mononucleosis usually resolve in 1 or 2 months, EBV dormant or latent in a few cells in the throat and blood for life.
T35	31266-31365	Epistemic_statement	denotes	Periodically, the virus can reactivate and is commonly found in the saliva of infected individuals.
T36	33308-33507	Epistemic_statement	denotes	Several studies have been published that claimed to identify oxacillin resistance of Staphylococcus aureus by whole cell matrix assisted laser desorption time of flight (MALDI-TOF) mass spectrometry.
T37	33652-33875	Epistemic_statement	denotes	Nevertheless, the study design in all of those studies was not suitable to achieve this goal, because only mecA/SCCmec isogenic strains could discriminate between strain specific-and mecA / SCCmec-dependent peak variations.
T38	34295-34375	Epistemic_statement	denotes	The loss of the mecA gene during freezing culture has been previously described.
T39	34656-34780	Epistemic_statement	denotes	In two out of 16 samples we could select a mecA containing strain and a corresponding isogenic strain lacking the mecA gene.
T40	35472-35724	Epistemic_statement	denotes	In contrast to several reports in literature, we could show for the first time that whole cell MALDI-TOF MS-derived peak profiles are not suitable for the discrimination of mecA positive S. aureus strains in the mass-to-chargeratio of 2000 to 15000 Da.
T41	36293-36403	Epistemic_statement	denotes	However, the resolution of complex mixtures, detection of antibiotic resistance markers are still unmet needs.
T42	36404-36662	Epistemic_statement	denotes	In order to overcome these limitations, a new molecular technology, PCR coupled to Mass Spectrometry, was developed, allowing detection and identification of multiple pathogens and selected antibiotic resistance markers or virulence factors in a single test.
T43	38474-38627	Epistemic_statement	denotes	Type II NADH dehydrogenases can occur either as internal enzymes, which utilize mitochondrial NADH, or as external enzymes, which utilize cytosolic NADH.
T44	38628-38849	Epistemic_statement	denotes	We determined the orientation of both isoforms by applying a split GFP complementation approach and could demonstrate that both isoforms are internal enzymes, which face with their active site to the mitochondrial matrix.
T45	39307-39524	Epistemic_statement	denotes	A functional complementation was possible by ectopic expression of the deleted gene, but not by expression of the heterologous isoform, suggesting that the two enzymes possess nonredundant, isotype-specific functions.
T46	41190-41326	Epistemic_statement	denotes	Additionally, no parasite-induced cell lysis could be observed in differentiated C2C12 in contrast to nondifferentiated C2C12 or NIH3T3.
T47	41620-41752	Epistemic_statement	denotes	Therefore, we also investigated whether MAPK might control T. gondii development in differentiated and undifferentiated C2C12 SkMCs.
T48	42187-42316	Epistemic_statement	denotes	Together, these results suggest that the host cell type and the differentiation of SkMCs regulate T. gondii replication in vitro.
T49	42317-42430	Epistemic_statement	denotes	This might also explain the different efficiencies of T. gondii to persist in differentiated tissues of the host.
T50	42431-43054	Epistemic_statement	denotes	The Candida albicans factor H binding molecule Hgt1p also functions as complement receptor 3 (CR3) and HIV binding molecule EKP07 Caenorhabditis elegans as a host model system to screen novel antifungal benzimidazole derivatives A. Singh* 1 , W. Abu Rayyan 1 , T. Dietsche 1 , H. Eickhoff 2 , K.-H. Wiesmüller 2 , K. Schröppel 1 1 Universitätsklinikum Tübingen, Interfakultäres Institut für Mikrobiologie und Infektionsmedizin, Tübingen, Deutschland 2 EMC microcollections GmbH , Tübingen, Deutschland Candida albicans, a commensal microorganism, is a causative agent of opportunistic oral and genital infections in humans.
T51	43130-43350	Epistemic_statement	denotes	Treatment of invasive fungal infections is problematic due to several persisting therapeutic drawbacks, in particular development of resistance against the currently available drugs or toxic side effects for the patient.
T52	43441-43596	Epistemic_statement	denotes	Previously, the nematode Caenorhabditis elegans has been successfully used as a model host for human pathogens and to screen for novel antimicrobial drugs.
T53	43597-43782	Epistemic_statement	denotes	It has been shown that C. albicans colonizes the intestinal tract of C. elegans and establishes a persistent lethal infection accompanied by deep tissue invasion of the entire organism.
T54	44760-44930	Epistemic_statement	denotes	During in vivo infection studies, we could demonstrate that EMC120B12 can inhibit filamentation of C. albicans and prolong survival of the C. albicans infected nematodes.
T55	44931-45181	Epistemic_statement	denotes	EMC120B12 identified in this screen can potentially be used as an effective antifungal agent and will be further investigated for its activity against other fungal species and also in a murine model to study its activity against systemic candidiasis.
T56	45581-45785	Epistemic_statement	denotes	However, these internal walls contain central pores allowing the exchange of molecules, nutrients and even organelles enabling the mycelium to respond as a functional entity to changes in the environment.
T57	45786-45907	Epistemic_statement	denotes	The draw-back of this organization is that a local damage of the cell wall is a potential threat for the whole syncytium.
T58	46060-46294	Epistemic_statement	denotes	In several fungi the Hex1 or HexA protein has been identified a major and essential component of the Woronin body and mutants generated in Neurospora crassa or Aspergillus oryzae show uncontrolled loss of cytoplasm after local damage.
T59	46295-46484	Epistemic_statement	denotes	Loss of Hex1 in Magnaporthe grisea impairs the virulence of this plant pathogen, but no data are yet available on the role of Hex proteins in filamentous fungi causing infections in humans.
T60	47483-47862	Epistemic_statement	denotes	Functional analysis of C. albicans infection-associated genes with unknown function during interaction with host cells and in complex infection models I. Jacobsen* 1 , D. Wilson 1 , F. Mayer 1 , B. Hube Mikrobielle Pathogenitätsmechanismen, Jena, Deutschland Introduction: Candida albicans is a common fungal pathogen in humans and able to cause a variety of clinical infections.
T61	47863-48050	Epistemic_statement	denotes	We hypothesized that C. albicans unknown function genes, which are transcriptionally upregulated during infection ("infection associated genes") might contribute to the infection process.
T62	48051-48165	Epistemic_statement	denotes	Aim and Methodology: We aimed to determine whether C. albicans infection associated genes contribute to virulence.
T63	48166-48374	Epistemic_statement	denotes	Therefore, based on transcriptional profiling from oral infections, liver invasion and incubation in human blood, we selected a subset of infection-associated genes with unknown function for further analysis.
T64	48375-48555	Epistemic_statement	denotes	Isogenic deletion mutants were constructed and subsequently tested in extensive in vitro screens, interaction with epithelial and endothelial cells and in complex infection models.
T65	48556-48708	Epistemic_statement	denotes	Results: Twentyfour isogenic deletion mutants were constructed and subsequently analyzed both in vitro and in infection models of increasing complexity.
T66	48965-49178	Epistemic_statement	denotes	To determine whether the deleted genes influenced virulence in more complex infections models, all 24 mutants were tested in ovo for their ability to kill chicken embryos infected on the chorio-allantoic membrane.
T67	49179-49359	Epistemic_statement	denotes	We recently showed that mortality in this model depends on the fungal ability to invade the membrane and that the pro-inflammatory host response likely contributes to pathogenesis.
T68	49360-49497	Epistemic_statement	denotes	Surprisingly, only seven mutants were attenuated in this model, of which five were also attenuated in damaging epithelial cells in vitro.
T69	49781-49993	Epistemic_statement	denotes	Discussion and Outlook: Our results demonstrate that genes essential for causing full damage of epithelial or endothelial cells in vitro are not necessarily crucial for full virulence in complex infection models.
T70	49994-50257	Epistemic_statement	denotes	We conclude that either such damage potential is not critical for full virulence in the complex host setting or that the greater complexity of the environment in animal models stimulates additional fungal regulatory networks leading to compensation of the defect.
T71	50258-50539	Epistemic_statement	denotes	Thiol-dependent redox networks: analysing the effects of the anti-malarial agent Methylene Blue Introduction: The development and spread of resistance against standard antimalarial drugs such as chloroquine (CQ) and pyrimethamine/sulfadoxin (PSD) has been a challenge for 25 years.
T72	52643-52759	Epistemic_statement	denotes	Conclusions: Taken together, our data suggest that MB could become a key factor in drug combination therapy efforts.
T73	52760-52834	Epistemic_statement	denotes	This should be tested more as a promising local eradication strategy [3] .
T74	54650-54797	Epistemic_statement	denotes	Interestingly, the tec1/tec1 phenotype was rescued in a mutant containing an ORF with an additional 72 aa that spanned the region from 1 to 709 aa.
T75	55555-55741	Epistemic_statement	denotes	Accumulating evidence indicates an involvement of RNA-binding proteins in regulating expression programmes underlying pathogenic development of the phytopathogenic fungi Ustilago maydis.
T76	56156-56313	Epistemic_statement	denotes	Khd4 recognizes a distinct hexanucleotide motif which is present in almost 25% of all annotated transcripts, suggesting a large regulatory potential of Khd4.
T77	56415-56478	Epistemic_statement	denotes	The precise role and function of Khd4 however is still unclear.
T78	57256-57345	Epistemic_statement	denotes	The high mortality of these infections is largely due to the limited therapeutic options.
T79	57346-57465	Epistemic_statement	denotes	Since A. fumigatus seems to lack sophisticated virulence traits, alternative therapeutic targets have to be identified.
T80	57555-57676	Epistemic_statement	denotes	Interference with signaling pathways helping the fungus to adapt to situations of stress is therefore a promising option.
T81	57677-57798	Epistemic_statement	denotes	However, this approach is hampered by the fact that many signaling pathways and molecules are conserved in fungi and men.
T82	58141-58236	Epistemic_statement	denotes	A similar protein architecture has recently been proposed to constitute an osmo-sensing module.
T83	58798-59059	Epistemic_statement	denotes	Mutants defective in genes of the cell wall integrity (CWI) pathway are significantly more sensitive to fludioxonil suggesting either a cross-talk between the HOG and the CWI pathway and/or a requirement for cell wall dynamics to bear fludioxonilinduced stress.
T84	60309-60441	Epistemic_statement	denotes	According to their homologues in S. cerevisiae, some of the genes deleted in mutants are presumably involved in cell wall integrity.
T85	60442-60631	Epistemic_statement	denotes	Since cell wall integrity is crucial for stress resistance and virulence, further analysis of deletion mutant strains which are predicted to be part of one signalling network was performed.
T86	61018-61223	Epistemic_statement	denotes	Similar behaviour could be observed while assaying cell wall stability and composition, with slg1 having considerably changed properties in comparison to the mutant strains mid2 and slt2 and the wild type.
T87	61224-61493	Epistemic_statement	denotes	Comparing the trancriptomes of the deletion strains with the wild type in the presence or absence of congo red showed only very slight changes in the expression pattern of mid2 and slt2, whereas in slg1 a significantly changed transcriptional profile could be detected.
T88	61494-61608	Epistemic_statement	denotes	The results obtained suggest that SLG1 has a different role in C. glabrata than in S. cerevisiae compared to MID2.
T89	61609-61741	Epistemic_statement	denotes	The function of the inspected genes of the cell wall integrity pathway in S. cerevisiae might therefore be different in C. glabrata.
T90	64333-64537	Epistemic_statement	denotes	Trypanosomal transmigration across the optimized ECV304-C6 model occurs in both directions underlining the possibility of a relapsing parasitemia after treatment with drugs that have no access to the CNS.
T91	64538-64711	Epistemic_statement	denotes	This model promotes the analysis of the cellular and molecular mechanisms underlying the CNS invasion, which is urgently needed for therapy improvement and drug development.
T92	65045-65225	Epistemic_statement	denotes	Tight junctional transmembrane proteins, notably claudins, regulate paracellular permeability of the intestinal barrier, constricting diffusion of small solutes and macromolecules.
T93	65226-65314	Epistemic_statement	denotes	Barrier function can be affected by pathogenic microorganisms, toxins and other stimuli.
T94	67440-67541	Epistemic_statement	denotes	Outlook: The results indicate an active participation of C. albicans in intestinal barrier breakdown.
T95	67542-67656	Epistemic_statement	denotes	However, the relative impacts of host and fungus on barrier disturbance will have to be clarified in ongoing work.
T96	68339-68604	Epistemic_statement	denotes	Immigrating immune cells are characterized by an increased glucose uptake, which can be used for non-invasive imaging: Fluorine labeled glucose (FDG -2-[ 18 F]fluoro-2-deoxy-D-glucose) is used as tracer for positron emission tomography/computer tomography (PET/CT).
T97	68605-68748	Epistemic_statement	denotes	Alternatively, a fluorescence labeled glucose derivative (RediJect 2-DG-750 Probe, Caliper) is detectable by the In-Vivo-Imaging-System (IVIS).
T98	68749-69064	Epistemic_statement	denotes	Since non invasive imaging tools to monitor inflammation have the potential to reduce the number of laboratory animals needed for the investigation of IA, we aimed to determine whether the above mentioned in vivo imaging systems are suitable for the quantification of the host's inflammatory response to IA in mice.
T99	71004-71310	Epistemic_statement	denotes	Zipfel 2 , C. Skerka 2 , G. Pradel 1 1 Research Center for Infectious Diseases, Würzburg, Deutschland 2 Leibniz Institute for Natural Product Research and Infection Biology, Jena, Deutschland As part of the innate immune system, the human complement is a first line of defence against microbial infections.
T100	72239-72376	Epistemic_statement	denotes	FH comprises 20 complement control protein modules, and binding of FH to malaria gametes appears to be primarily mediated by modules 1-7.
T101	72720-72812	Epistemic_statement	denotes	Our findings might lead to novel approaches in the design of transmission blocking vaccines.
T102	72813-72908	Epistemic_statement	denotes	Up to now there is only little data on the interaction of human NKC with the pathogenic fungus.
T103	72909-73013	Epistemic_statement	denotes	However, after NKC depletion mice have been shown to be more susceptible to systemic Candida infections.
T104	73014-73148	Epistemic_statement	denotes	On the basis of these observations we investigated if there are direct or indirect effects of human NK Cells against Candida albicans.
T105	74816-74945	Epistemic_statement	denotes	Blocking experiments suggest that the cytotoxic effect is perforin dependent while FasL/TRAIL receptor pathways are not involved.
T106	74946-75104	Epistemic_statement	denotes	In parallel to these direct effects, NKC may interact with other immune cells since cytokine release shows an upregulation of neutrophil activating cytokines.
T107	75105-75231	Epistemic_statement	denotes	Conclusions: Our observations suggest that NKC may play an important role in the first line defense of C. albicans infections.
T108	75232-75330	Epistemic_statement	denotes	In this context, direct and indirect antifungal effects of NKC are currently further investigated.
T109	75615-75773	Epistemic_statement	denotes	Although the incidence of fungal sepsis has increased recently, diagnosis is still difficult and mainly relies on the detection of the pathogen (Candida spp.)
T110	75955-76066	Epistemic_statement	denotes	These analyses will allow identifying immune markers which might be potentially useful in clinical diagnostics.
T111	76389-76501	Epistemic_statement	denotes	Further investigation included the characterisation of the whole blood transcriptome in response to C. albicans.
T112	76502-76653	Epistemic_statement	denotes	The obtained data will be integrated using bioinformatic methods to generate a network of innate immune activation during early steps of fungal sepsis.
T113	77018-77128	Epistemic_statement	denotes	As expected, myeloperoxidase from primary and lactoferrin from secondary granules could be detected in plasma.
T114	78046-78181	Epistemic_statement	denotes	Advantages over isolated primary cells are the physiological conditions and the possible communication between immune cell populations.
T115	78411-78460	Epistemic_statement	denotes	Protozoans like Leishmania can undergo apoptosis.
T116	78761-78914	Epistemic_statement	denotes	However, the protein machinery mediating apoptosis in mammalian cells like caspases or members of the bcl-2 families are completely absent in Leishmania.
T117	80365-80561	Epistemic_statement	denotes	In recent years, there has been increasing evidence for the occurrence of PCD in distinct unicellular organisms as well, however, there is only little information about putative PCD in Toxoplasma.
T118	80562-80690	Epistemic_statement	denotes	Therefore, identification of apoptosis-like markers and molecules that might play a role in T. gondii PCD need to be elucidated.
T119	82067-82207	Epistemic_statement	denotes	In order to unravel possible functions of T. gondii BI proteins in regulation of apoptosis, we heterologously expressed TgBIs in HeLa cells.
T120	82866-83012	Epistemic_statement	denotes	These findings suggest the existence of apoptotic-like cell death in T. gondii and protective effects of TgBI proteins in regulation of apoptosis.
T121	83410-83637	Epistemic_statement	denotes	Infection of individuals with premature or suppressed immunity can lead to lifethreatening toxoplasmosis whereas in immune competent hosts, infection is mostly asymptomatic but leads to parasite persistence for the host's life.
T122	83638-83758	Epistemic_statement	denotes	Cell-mediated immunity including the production of IFN-is critical for control of the obligatory intracellular parasite.
T123	83759-83968	Epistemic_statement	denotes	However, by using genomewide transcriptome analysis, we have shown that T. gondii leads to global unresponsiveness of murine macrophages to IFN-and this may be essential for establishing a long-term infection.
T124	85113-85306	Epistemic_statement	denotes	Together, these data unravel novel insights into the mechanisms by which T. gondii evades IFN-regulated immunity and open up novel strategies for therapeutic intervention against toxoplasmosis.
T125	86753-87163	Epistemic_statement	denotes	In biofilm assays, the full length TEC1 ORF was able to restore the ability for biofilm formation ability in the tec1/tec1 mutant background after Tet induced gene expression, and the biofilm mass was similar to the biofilm formed by the wild type SC5314 strain, whereas the TEA domain mutant and mutants lacking the proposed C-terminal motif were impaired in biofilm formation under similar growth conditions.
T126	87324-87555	Epistemic_statement	denotes	Further in vivo investigations with C. elegans infection model revealed that the C. albicans TEC1 mutant lacking this C-terminal motif shows less virulence against nematodes in terms of hyphal invasion and killing of the nematodes.
T127	87816-87985	Epistemic_statement	denotes	It can be demonstrated that this C-terminal motif of Tec1p is essential for yeast-hyphae transition, infection and killing of C. elegans nematodes and biofilm formation.
T128	88039-88263	Epistemic_statement	denotes	Scharf 1 1 Universitätsklinikum Düsseldorf, Institut für Hämostaseologie und Transfusionsmedizin, Düsseldorf, Deutschland Introduction: Candida albicans is a dimorphic fungus that can switch between the yeast and hypha form.
T129	88349-88408	Epistemic_statement	denotes	Platelets can bridge the innate with the adaptive immunity.
T130	88516-88654	Epistemic_statement	denotes	Platelet integrins and their plasma ligands can govern both binding to the pathogen and activation of platelets to release their granules.
T131	88655-88836	Epistemic_statement	denotes	Here we tested the hypothesis that fibronectin (which is also stored in platelet -granular and bound by platelet integrins) supports the host defense against C. albicans infections.
T132	90319-90484	Epistemic_statement	denotes	Hence, platelets and fibronectin, with its intrinsic multivalent binding site can support the platelet mediated host defense and immune response against C. albicans.
T133	90835-91298	Epistemic_statement	denotes	Its central MAP kinase module was subject of diverse studies and is conserved from Saccharomyces cerevisiae to filamentous fungi, such as Aspergillus spp.. On the contrary, components upstream of this MAP kinase module are well characterized in S. cerevisiae but largely unknown in Aspergillus spp.. We have identified, localized and functionally characterized homologues of the S. cerevisiae cell surface sensors ScWsc1 -ScWsc3 and ScMid2/ScMtl1 in A. fumigatus.
T134	91551-91691	Epistemic_statement	denotes	In addition, our data indicate fundamental functional differences on the sensor level of the CWI pathways of S. cerevisiae and A. fumigatus.
T135	91692-92176	Epistemic_statement	denotes	Trends in multidrug resistance among Escherichia coli and klebsiellae in Germany M. Kresken* 1,2 , D. Hafner 2,3 1 Antiinfectives Intelligence GmbH, Rheinbach, Deutschland 2 Paul-Ehrlich-Gesellschaft für Chemotherapie e.V., Rheinbach, Deutschland 3 Institute for Pharmacology and Clinical Pharmacology, Heinrich-Heine-University, Düsseldorf, Deutschland Introduction: Escherichia coli (ECO) and klebsiellae are among the most common pathogens causing infections in in-and outpatients.
T136	92177-92334	Epistemic_statement	denotes	Antimicrobial agents such as 3rd generation cephalosporins (3GC), carbapenems (carba) and fluoroquinolones (FQ) are essential drugs to treat serious illness.
T137	92335-92499	Epistemic_statement	denotes	Treatment outcome, however, has increasingly been threatened by the emergence and dissemination of resistant (R) strains (multi-drug R [MDR] strains in particular).
T138	99328-99502	Epistemic_statement	denotes	pathogens in Germany, all clinically used dosing regimens of CARBA are sufficient to achieve a probability of 95% or greater success against CRO-resistant Enterobacteriaceae.
T139	101794-101897	Epistemic_statement	denotes	However, there was an alarming increase of ESBL rates in outpatients from 1.3% in 2007 to 5.9% in 2010.
T140	102066-102126	Epistemic_statement	denotes	Probably the outbreak was caused by contaminated vegetables.
T141	103068-103165	Epistemic_statement	denotes	The isolated displayed an ESBL phenotype and blaTEM-1 as well as blaCTX-M-15 could be identified.
T142	103548-103635	Epistemic_statement	denotes	No co-resistance to tetracycline or sulfamethoxazoletrimethoprim could be demonstrated.
T143	103636-103838	Epistemic_statement	denotes	Conclusion: Within two days after receipt of the EHEC outbreak isolate the molecular basis of its unusual ESBL phenotype could be clarified and was immediately reported to the German health authorities.
T144	103905-104096	Epistemic_statement	denotes	The presence of resistance genes in diarrheagenic bacterial strains is worrisome since it might contribute to an enhanced spread of resistance determinants, e. g. by horizontal gene transfer.
T145	104371-104473	Epistemic_statement	denotes	Data on the in vitro susceptibility of pathogens isolated from ocular infections, however, are scarce.
T146	106823-106975	Epistemic_statement	denotes	Carbapenem resistance in P. aeruginosa can be caused by a variety of mechanisms, however the worldwide spread of carbapenemases is especially important.
T147	108347-108461	Epistemic_statement	denotes	An unspecific result due to toxicity of EDTA could be excluded by a positive bioassay based on cell-free extracts.
T148	108861-109010	Epistemic_statement	denotes	It clearly shows a MBL phenotype, while the MIC differences for imipenem are likely to be the result of additional mechanism for imipenem resistence.
T149	109802-109906	Epistemic_statement	denotes	However, the correct identification of carbapenemases is challenging for the microbiological laboratory.
T150	110177-110266	Epistemic_statement	denotes	A bioassay based on cell-free extracts allows the detection of still unknown -lactamases.
T151	110517-110833	Epistemic_statement	denotes	Several different carbapenemases could be detected, including OXA-48 (n = 59), KPC-2 (n = 31), KPC-3 (n = 26), VIM-1 (n = 37), VIM-2 (n = 20), VIM-4 (n = 4), VIM-5 (n = 1), IMP-7 (n = 2), IMP-8 (n = 12), IMP-16 (n = 1), NDM-1 (n = 5), NDM-2 (n = 1), GIM-1 (n = 4), OXA-23 (n = 69), OXA-72 (n = 2) and OXA-58 (n = 6).
T152	111106-111294	Epistemic_statement	denotes	However, the molecular epidemiology in Germany with a predominance of OXA-48 differs significantly from observations made in other countries like Greece, Israel, USA or the United Kingdom.
T153	111410-111589	Epistemic_statement	denotes	Objectives: The successful worldwide dissemination of carbapenemase producing Enterobacteriaceae is of special concern because of limited therapeutic options and higher mortality.
T154	111590-111900	Epistemic_statement	denotes	While the dissemination of carbapenemase KPC is predominantly bound to distinct Klebsiella pneumoniae strains, spread of OXA-48 and NDM-1 enzymes is mainly due to conjugative transfer of different plasmids carrying these carbapenemase genes and facilitating the transmission among many enterobacterial species.
T155	113489-113687	Epistemic_statement	denotes	Although carbapenemase producing Enterobacteriaceae are still rare in many European countries there is an urgent need of surveillance to prevent further spread of these multidrugresistant pathogens.
T156	113688-113769	Epistemic_statement	denotes	How should we treat double -and triple -resistant Helicobacter pylori in Germany?
T157	113770-113903	Epistemic_statement	denotes	Background and Objective: Enterobacteriaceae have been shown to play a crucial role in the transmission of antimicrobial resistances.
T158	114025-114306	Epistemic_statement	denotes	Dissemination of antibiotic resistance can be due to the transfer of resistant bacteria between different host organisms or by horizontal transfer of resistance properties between isolates of the same or different species and genera within and beyond the family Enterobacteriaceae.
T159	114307-114629	Epistemic_statement	denotes	Especially, resistance to -lactams mediated by production of Extended-spectrum beta-lactamases (ESBL) and resistance to (fluoro)quinolones influenced by different plasmid-mediated quinolone resistance determinants are of concern since they limit dramatically the therapeutic options in both, veterinary and human medicine.
T160	115850-116067	Epistemic_statement	denotes	The RESET network includes different interacting and complementary studies on factors associated with the dissemination of emerging resistance properties in Enterobacteriaceae from humans, animals and the environment.
T161	117049-117231	Epistemic_statement	denotes	Our data show frequent co-resistances to therapeutically relevant antibiotics (ampicillin, aminoglycosides) for enterococci; resistances to antibiotics of last resort are still rare.
T162	117232-117331	Epistemic_statement	denotes	Comparably high rates of vanB VRE suggest a changing epidemiology of van genotypes in recent years.
T163	117695-117791	Epistemic_statement	denotes	Therefore, testing the activity of older and rarely used antibiotics is of high clinical impact.
T164	119012-119194	Epistemic_statement	denotes	Applying a threshold of 16 mm as susceptible in disk diffusion (fosfomycin 200 μg) as recommended by CLSI for E. coli eleven very major errors (10.3%) and no major errors were found.
T165	120326-120513	Epistemic_statement	denotes	Based on the whole genome data the mprF locus, which was previously shown to be associated with daptomycin resistance was re-sequenced in 64 daptomycin resistant and susceptible isolates.
T166	120886-120995	Epistemic_statement	denotes	Sequence analysis of whole genome data revealed a small number of SNPs putatively associated with resistance.
T167	120996-121203	Epistemic_statement	denotes	However, after re-sequencing the corresponding loci in a larger number of resistant and susceptible isolates strong association of resistance to mutations in a certain locus could be confirmed only for mprF.
T168	121301-121502	Epistemic_statement	denotes	Conclusion: Results corroborate the role of mprF-mutations in resistance development towards daptomycin; however further studies must elucidate the complete mechanism leading to reduced susceptibility.
T169	121975-122027	Epistemic_statement	denotes	Data regarding carbapenemases in Germany are scarce.
T170	123180-123364	Epistemic_statement	denotes	Transconjugation experiments were successful only in one strain, however the presence of blaKPC on plasmids could be demonstrated by restriction with S1 endonuclease and Southern Blot.
T171	123656-123763	Epistemic_statement	denotes	The low MIC for carbapenems in some strains emphasizes that detection of carbapenemases can be challenging.
T172	124174-124394	Epistemic_statement	denotes	In this context it is of interest whether czrC and the already known resistance gene cadA (both code for an ATPase based efflux) are disseminated among different clonal lineages of MRSA prevalent in humans and livestock.
T173	124695-124910	Epistemic_statement	denotes	Results: czrC was exclusively associated with MRSA ST398 (20/27 from pigs; 21/23 from humans exposed to pigs; 10/20 infections; 10/10 infections in humans) and contained by a defined SCCmec-element with tandem ccrC.
T174	125349-125536	Epistemic_statement	denotes	Discussion: It can not be excluded that the previous use of zinkoxide ions in conjunction with organic acids as feed additives has selected for czrC and possibility coselected MRSA ST398.
T175	125781-125986	Epistemic_statement	denotes	With respect to multiresistant but methicillin susceptible S. aureus ST30 ("80/80 complex") in the past and use of zinkoxide ointments containing also boronic acid this situation might have been different.
T176	125987-126160	Epistemic_statement	denotes	Introduction: The emergence of healthcare associated infections caused by multidrug-resistant Gram-negative bacteria has become an increasing problem over the past 20 years.
T177	126161-126296	Epistemic_statement	denotes	Colistin, a 'forgotten' antibiotic, has attracted attention, because of its activity against multidrug-resistant Gramnegative bacteria.
T178	126297-126358	Epistemic_statement	denotes	It is, however, not active against Proteeae and Serratia spp.
T179	128351-128453	Epistemic_statement	denotes	Conclusions: Overall, susceptibility to COL seems to be high among Gram-negative pathogens in Germany.
T180	128454-128509	Epistemic_statement	denotes	COL may be considered as an important treatment option.
T181	129717-129801	Epistemic_statement	denotes	MIC to penicillin depended on serogroup: using serogroup B and rare serogroups (e.g.
T182	129983-130075	Epistemic_statement	denotes	Interestingly, 51.9% of serogroup W-135 strains were intermediate susceptible to penicillin.
T183	130192-130341	Epistemic_statement	denotes	Although no resistance was observed for cefotaxime, cefotaxime MICs showed a weak yet significant linear correlation with penicillin MICs (r^2 0.23).
T184	130490-130629	Epistemic_statement	denotes	Due to low rate of nonsusceptibility, no meaningful analyses were possible for antimicrobials rifampicin and ciprofloxacin in meningococci.
T185	130779-130928	Epistemic_statement	denotes	Resistance was significantly more common in non-typeable H. influenzae lacking a polysaccharide capsule (13.0%) compared to capsulate strains (3.7%).
T186	133443-133860	Epistemic_statement	denotes	Discussion: While the EARS-Net-Surveillance limited to invasive isolates from hospitalised patients captures the sector with highest levels of antimicrobial resistance in K. pneumoniae, the extended approach of ARS reveals an emerging problem in outpatient care that physicians should be aware of, even if resistance proportions might be overestimated as samples are more likely to be taken from pre-treated patients.
T187	135252-135291	Epistemic_statement	denotes	451 patients have been examined so far.
T188	135680-135847	Epistemic_statement	denotes	19% of the patients were still H. pylori positive after treatment, which might be explained by the high rate of clarithromycin resistance (29%) within this population.
T189	135848-136040	Epistemic_statement	denotes	In conclusion, these results underline the hypothesis that development of resistance in H. pylori in contrast to other pathogens is dependent on treatment strategies in the individual patient.
T190	136486-136736	Epistemic_statement	denotes	Stratification by federal states shows considerable regional differences (range:1.8-6.4/100,000 inhabitants/year), which were positively correlated to regional MRSA-rates (6.7%-27.3%) generated in ARS (spearman correlation coefficient: 0.74; p=0.04).
T191	136737-136912	Epistemic_statement	denotes	Conclusion: While mandatory reporting of MRSA-bacteraemia serves as an indicator of the situation in hospital care, ARS additionally provides a view on the outpatient setting.
T192	137005-137117	Epistemic_statement	denotes	Nevertheless, the results indicate that in Germany MRSA plays a relevant role in the outpatient setting as well.
T193	137118-137367	Epistemic_statement	denotes	Particularly, high resistance rates in urine samples suggest that further investigations about the epidemiological context in which infections occur and patient characteristics are necessary to assess possible consequences for antibiotic management.
T194	137590-138007	Epistemic_statement	denotes	Wieler 1 , C. Ewers 1 1 Freie Universität Berlin, Institut für Mikrobiologie u. Tierseuchen, Berlin, Deutschland 2 Vet Med Labor GmbH, Ludwigsburg, Halle, Deutschland Introduction: Several studies give evidence for the carriage of Extendedspectrum beta-Lactamases (ESBL) producing E. coli in the feces of wild birds even in remote areas, where the presence of antibiotic selection pressure is assumed to be very rare.
T195	138708-138909	Epistemic_statement	denotes	Genotyping led to the frequent detection of virulence determinants associated with extraintestinal pathogenicity whereas genes associated with intestinal pathogenic pathovars were only rarely observed.
T196	139172-139369	Epistemic_statement	denotes	Among the Mongolian samples we identified several STs, such as ST167 (ancestral group A) or ST648 (hybrid group ABD) which have previously been reported from human clinical ESBL producing isolates.
T197	139596-139732	Epistemic_statement	denotes	Conclusions: Our findings underline the urgent need to unravel the role of wild birds in the spread of antimicrobial resistant bacteria.
T198	139733-139998	Epistemic_statement	denotes	Due to their migration behavior and with respect to the omnipresence of bird´s feces in wild and urban environments, wild birds might represent a non-point source of infection and could by that considerably contribute to the transmission of ESBL producing bacteria.
T199	140564-140738	Epistemic_statement	denotes	The currently used methods require the use of experts to evaluate the result of noise removal, because the methods need some parameters which correlate to the detected noise.
T200	140739-140805	Epistemic_statement	denotes	The adaption/calibration can only be executed by a manual process.
T201	140899-141042	Epistemic_statement	denotes	The focus of this article lies in the development of automated pre-processing method which can reduce the significantly influence of the noise.
T202	141043-141134	Epistemic_statement	denotes	Noise: Generally, in test results, two different types of noise can occur (Wilhelm, 2003) .
T203	141236-141295	Epistemic_statement	denotes	The possible causes of the occurrence are not yet resolved.
T204	141296-141419	Epistemic_statement	denotes	The effects of background noise and signal trend for the repeated execution of sample analysis may lead to varying results.
T205	143535-143678	Epistemic_statement	denotes	Results: Comparing Ulifloxacin vs. Ciprofloxacin and Norfloxacin concordant results could be obtained in 250 of the 267 (93.6%) tested strains.
T206	144320-144464	Epistemic_statement	denotes	For Enterococci following results could be found: Susceptibility to Ciprofloxacin, Norfloxacin and Prulifloxacin was 38%, 42%, 28% respectively.
T207	144559-144694	Epistemic_statement	denotes	Comparing the results of Ciprofloxacin, Norfloxacin and Ulifloxacin concordant results in 250 of 267 strains (93.6%) could be obtained.
T208	144786-144947	Epistemic_statement	denotes	Against gram positive strains Ulifloxacin was slightly less active as Ciprofloxacin and Norfloxacin, but this statement is limited by the low number of isolates.
T209	144948-145172	Epistemic_statement	denotes	Because of some minor differences in the interpretation of the susceptibility pattern testing of Ulifloxacin and/or other chinolones resistance testing seems to be noteworthy if therapy with this fluorochinolone in intended.
T210	145173-145503	Epistemic_statement	denotes	Impact of thymidine on the antimicrobial activities of trimethoprim/sulfamethoxazole, 5-iodo-2'-deoxyuridine, and rifampicin against Staphylococcus aureus Objectives: A treatment option against S. aureus in general and MRSA in particular is trimethoprim/sulfamethoxazole (SXT) either alone or in combination with rifampicin (RIF).
T211	145667-145878	Epistemic_statement	denotes	However, the antimicrobial activity of SXT can be antagonised by bacterial utilisation of thymidine, which can be present in infected and/or inflamed tissues such as the airways of cystic fibrosis (CF) patients.
T212	145879-146132	Epistemic_statement	denotes	The aim of this study was to determine thymidine concentrations in the sputa of CF patients and to analyse the antimicrobial activity of SXT, 5-iodo-2´-deoxyuridine (IdUrd) and RIF alone and in combination against S. aureus in the presence of thymidine.
T213	146906-147073	Epistemic_statement	denotes	Conclusions: Our data suggest that SXT in combination with rifampicin may fail to cure clinical S. aureus infections in tissues with elevated thymidine concentrations.
T214	147074-147220	Epistemic_statement	denotes	SXT in combination with a thymidine kinase inhibitor, however, may become an interesting antimicrobial combination for this setting in the future.
T215	147282-147582	Epistemic_statement	denotes	Non-nucleoside analogs as bacterial thymidine kinase inhibitors identified by multi-step virtual screening Objectives: The antimicrobial activity of folic acid antagonists can be antagonized by thymidine as detected in tissues with necrotic cells such as pus and sputum from cystic fibrosis patients.
T216	147792-148025	Epistemic_statement	denotes	However, several bacterial species including S. aureus possess an alternative pathway for synthesis of intracellular dTMP by uptake of extracellular thymidine and subsequent intracellular phosphorylation to dTMP via thymidine kinase.
T217	148844-149023	Epistemic_statement	denotes	Conclusions: Our study demonstrates that multi-step virtual screening can help identify bioactive substances from a large screening compound pool with limited experimental effort.
T218	149024-149182	Epistemic_statement	denotes	Rapid focusing on promising candidate structures was possible, so that inhibitors of bacterial thymidine kinase with non-nucleoside scaffolds were identified.
T219	149615-149915	Epistemic_statement	denotes	Schmidt 1 1 ZMBE, Infektiologie, Münster, Deutschland 2 UKM, Institute of Experimental Musculoskeletal Medicine, Münster, Deutschland Cell-permeable proteins such as 'cell-penetrating peptides (CPP)' have the ability to cross cellular membranes, either alone or in association with a bioactive cargo.
T220	150244-150379	Epistemic_statement	denotes	This might contribute to systemic effects on innate immunity and, furthermore, suggests potential therapeutic applications of YopM e.g.
T221	150414-150719	Epistemic_statement	denotes	Hence, we were interested to investigate whether YopM might have the potential to act as an immune modulating molecule by exhibiting beneficial effects on inflammation and the production of cytokines that maintain the inflammatory processes linked to autoimmune diseases such as rheumatoid arthritis (RA).
T222	151256-151354	Epistemic_statement	denotes	With respect to a potential in vivo application of YopM, we injected YopM intra-articularly (i.a.)
T223	152114-152358	Epistemic_statement	denotes	These encouraging results combined with the possibility for focused topical applications in skeletal joints underline and strengthen the potential of YopM as a novel pathogen-derived immune modulatory agent for the treatment of inflammatory RA.
T224	152359-152693	Epistemic_statement	denotes	Comparison of genotypic, proteotypic and phenotypic methods for the identification of bacteria M. Patel 1 , U. Herber* 1 1 Accugenix, Marketing, Newark, Deutschland Accurate classification of unknown bacterial isolates is an essential first step in understanding the impact these organisms have on an environmental monitoring program.
T225	152694-152914	Epistemic_statement	denotes	There are many methods, technologies, and strategies utilized to determine the identity of unknown microorganisms, however, the selection of these methods is often impacted by more than the performance of the technology.
T226	153331-153471	Epistemic_statement	denotes	When identifications are based on phenotypic characteristics, the methods are more subjective and results can be impacted by many variables.
T227	154115-154219	Epistemic_statement	denotes	These microbial identification methods were used to analyze 60 unknown environmental bacterial isolates.
T228	154946-155014	Epistemic_statement	denotes	The pathogenesis of psoriasis is complex and not clearly understood.
T229	155015-155129	Epistemic_statement	denotes	Ongoing research indicates that immune T-cells appear to play a dominant role for the development of this disease.
T230	155919-156017	Epistemic_statement	denotes	Therefore, YopM might be applicable as a topical therapeutic agent for the treatment of psoriasis.
T231	156018-156183	Epistemic_statement	denotes	To investigate whether YopM might be functional as an immune-modulator for the treatment of psoriasis, we utilized the murine imiquimod (IMQ)induced psoriasis model.
T232	156344-156449	Epistemic_statement	denotes	Therefore, this model could serve for the analysis of pathogenic mechanisms in psoriasis-like dermatitis.
T233	157522-157662	Epistemic_statement	denotes	The genomic island is integrated within the tRNA Pro gene (lpc2778) and can exist in an integrated chromosomal or an episomal circular form.
T234	157852-157976	Epistemic_statement	denotes	By deleting the int-1 gene, we could demonstrate that the excision and forming of an episomal circle is integrase dependent.
T235	157977-158149	Epistemic_statement	denotes	First experiments with a mutant lacking the vir region, also indicate a growth dependent regulation of the alteration between the integrated and the circular form of Trb-1.
T236	158150-158294	Epistemic_statement	denotes	The whole genomic island can be transferred to other Legionella strains and integrated site-specifically into the genome of the transconjugants.
T237	158979-159114	Epistemic_statement	denotes	We could demonstrate that both genomic islands can exist in an integrated chromosomal and an exercised episomal form, similar to Trb-1.
T238	159862-160065	Epistemic_statement	denotes	Although a substantial amount of information about the GSLreceptors for Shiga toxins (Stxs), the major virulence factors of EHEC, is available, less is known about the receptors for EHEC bacterial cells.
T239	160730-160929	Epistemic_statement	denotes	In the present study the potential of GSL recognition by various EHEC O157 strains was investigated employing neutral GSLs and sialylated GSLs (=gangliosides) from different types of mammalian cells.
T240	161549-161773	Epistemic_statement	denotes	In conclusion, this study may help to better understand host-pathogen interactions and in particular the adhesion process of EHEC toward target cells and, moreover, to develop strategies to prevent and treat EHEC infections.
T241	162800-163002	Epistemic_statement	denotes	Microdomain association of GSLs is believed to be the linchpin in effective binding, internalization and subcellular routing of GSL-binding AB5-toxins such as Shiga toxin (Stx) to intracellular targets.
T242	163796-163944	Epistemic_statement	denotes	Studies on the subcellular distribution of Stx receptors in both cell types showed their predominant association with and enrichment in lipid rafts.
T243	167345-167467	Epistemic_statement	denotes	These promising initial data suggest further characterization of the compounds and an evaluation of putative applications.
T244	167818-168112	Epistemic_statement	denotes	EF-Tu from Escherichia coli has been shown to polymerize in vitro and a recent study provided evidence that the protein serves besides its function in translation another vital role in Bacillus subtilis: it affects cell morphology, apparently via interaction with the cytoskeleton protein MreB.
T245	168113-168236	Epistemic_statement	denotes	In rod-shaped bacteria the actin-ortholog MreB is thought to direct incorporation of cell wall material into the side wall.
T246	168237-168395	Epistemic_statement	denotes	Surprisingly, chlamydiae harbor, despite their spherical shape and the absence of a cell wall, MreB and we recently proved in vitro activity for this protein.
T247	168607-168732	Epistemic_statement	denotes	Additionally, co-polymerization assays revealed interactions between the elongation factor and the cytoskeletal protein MreB.
T248	169235-169337	Epistemic_statement	denotes	This ubiquitous bacterium can cause two forms of legionellosis -Legionellapneumonia and Pontiac fiver.
T249	169446-169649	Epistemic_statement	denotes	Although the failure in the therapy occurs from time to time, there are no reports about the isolation of the macrolide or quinolon-resistant Legionella mutants from the patients and environment to date.
T250	170615-170775	Epistemic_statement	denotes	The reduced ecological fitness of the macrolide resistant mutants might be an explanation for the lack occurrence of resistant strains under natural conditions.
T251	170776-170955	Epistemic_statement	denotes	For more than a hundred years, it has been known that patients with solid tumors who concomitantly suffer from a bacterial infection experience a regression of their tumor burden.
T252	170956-171048	Epistemic_statement	denotes	Still, the phenomenon of bacterial tumor targeting and lysis remains only poorly understood.
T253	171234-171360	Epistemic_statement	denotes	Amid several theoretically interesting approaches, we focused our efforts on immunosuppressive and pro-inflammatory cytokines.
T254	171361-171547	Epistemic_statement	denotes	The immunosuppressive cytokines are supposed to expand the inoculum in the tumor and should enable the bacteria to penetrate the host immune defense shielding the tumor from total lysis.
T255	171548-171712	Epistemic_statement	denotes	On the other hand, the proinflammatory cytokines should attract inflammatory cells, boost NK cell and CD8+ T-cell activity and eventually lead to tumor vaccination.
T256	171713-171845	Epistemic_statement	denotes	Here, we are going to present first results with recombinant Interleukin-10 and Interleukin-12 fusion proteins expressed in E. coli.
T257	173422-173545	Epistemic_statement	denotes	However, while EDTA has found widespread application as a conservative, its clinical use is hampered by toxic side effects.
T258	174995-175200	Epistemic_statement	denotes	As this antibiotic has been in clinical use over the last 50 years without serious side effects having been reported, it constitutes a promising candidate for the development of new therapeutic strategies.
T259	175503-175610	Epistemic_statement	denotes	Their mutual agreement and factors influencing the results have not been studied in detail in South Africa.
T260	175611-175734	Epistemic_statement	denotes	Thus a study was conducted at 15 sampling sites in the Eastern Cape Province of South Africa to address this knowledge gap.
T261	177164-177302	Epistemic_statement	denotes	If a suspension of the sediment matter on-site took place, this would lead to a change in the bacterial concentrations between 0 and 24 %.
T262	177507-177618	Epistemic_statement	denotes	Conclusions: Re-suspension of sediment particles can compromise the results of microbial water quality testing.
T263	177619-177797	Epistemic_statement	denotes	Temperature fluctuations between 10 and 32 ºC are not expected to influence the applicability of the hydrogen-sulphide test in detection of faecal contamination of surface water.
T264	178536-178766	Epistemic_statement	denotes	A sustainable in-time management of emulsion paint production should rely on fast quantitative MC analysis of products and their effective separation, thereby minimizing preservative input and waste of contaminated emulsion paint.
T265	180392-180548	Epistemic_statement	denotes	Conclusions: Further development effort would be needed to optimize sample preparation with special focus on removal of inhibitory emulsion paint compounds.
T266	180549-180715	Epistemic_statement	denotes	All methods should run on (or must easily be adaptable to) integrated sample and analysis robotics applying qRT-PCR, automated analysis and interpretation of results.
T267	180716-180922	Epistemic_statement	denotes	This requirement is crucial since a final qRT-PCR based QC strategy should be able to manage the emulsion paint production without interaction of human PCR experts in a model environment at JWO in Coesfeld.
T268	181308-181454	Epistemic_statement	denotes	By performing studies on the interactions present in multispecies biofilms, basic knowledge on several aspects of sociomicrobiology can be gained.
T269	181455-181577	Epistemic_statement	denotes	The aim of this work was to assess the role of interspecies interactions in species biofilm formation and characteristics.
T270	182722-182875	Epistemic_statement	denotes	A range of interactions has been observed among microorganisms in biofilms, including competitive, mutualistic, antagonistic and commensal relationships.
T271	184188-184334	Epistemic_statement	denotes	These proteins are presumably highly antigenic due to the exposure to the host's immune system and may be used as antigens in diagnostic purposes.
T272	184335-184556	Epistemic_statement	denotes	In this study could be demonstrated that recombinantely produced Cj0069, one of the secreted proteins, has a similar sensitivity and specificity compared to the already and commercially established antigens OMP18 and P39.
T273	185982-186193	Epistemic_statement	denotes	Conclusion: This study reveals that hreP and the pyp genes are part of a complex regulatory network that is repressed by H-NS, further underlining our hypothesis that these genes have been acquired horizontally.
T274	187135-187333	Epistemic_statement	denotes	Depending on the serovar, host species, age and immune status the course of disease can range from asymptomatic carriage or localized acute diarrhea to severe systemic infections with fatal outcome.
T275	187334-187673	Epistemic_statement	denotes	To evaluate possible host differences in flagellin recognition in human and animal cells and subsequent induction of immunostimulatory signalling cascades, we have used the activation of transcription factor nuclear factor -B (NF-B) in NF-B reporter cell lines of different species origins that express a luciferase during NF-B activation.
T276	188188-188370	Epistemic_statement	denotes	The varying behaviour and sensing of Salmonella flagellin in different host species might contribute to the different outcome of infection and host adaptation of Salmonella serovars.
T277	188371-188537	Epistemic_statement	denotes	Shiga toxins (Stxs) are secreted by Stx-producing Escherichia coli (STEC) that cause diarrhea, bloody diarrhea and potentially lethal hemolytic-uremic syndrome (HUS).
T278	188930-189211	Epistemic_statement	denotes	Although preferential Stxmediated damage of glomerular microvascular endothelial cells (GMVECs) is known as the major mechanism underlying HUS caused by STEC, the exact nature of the Stx receptor GSLs of GMVECs including the expression of different lipoforms remains to be defined.
T279	190323-190424	Epistemic_statement	denotes	This higher sensitivity of GMVECs correlated with the enhanced expression of Stx-receptors in GMVECs.
T280	190425-190863	Epistemic_statement	denotes	However, as GSLs are believed to localize abundantly in lipid rafts tightly associated with cholesterol and raftassociated membrane proteins and since lipid raft association of Stx receptors is assumed as a functional prerequisite for Stx-mediated cytotoxicity, future investigations on the subcellular distribution of GSLs in GMVECs are required to explore the functional role of the molecular assembly of GSLs in microdomains of GMVECs.
T281	191196-191355	Epistemic_statement	denotes	Together with the CagA effector protein, it is encoded on the cag pathogenicity island (cag-PAI), the presence of which is associated with more severe disease.
T282	191819-191915	Epistemic_statement	denotes	Therefore, it is likely that H. pylori is able to modulate the immune response to its advantage.
T283	192001-192149	Epistemic_statement	denotes	It has been shown before that macrophages aggregate under the influence of the Cag T4SS, and that CagA can be translocated into these cells as well.
T284	192624-192774	Epistemic_statement	denotes	The migration assays suggest that H. pylori infection results in a chemotactic defect of phagocytic cells and in an inhibition of phagocyte migration.
T285	192775-192912	Epistemic_statement	denotes	Infection with H. pylori mutants showed that the inhibitory effect on human granulocyte migration is likely to be caused by the Cag T4SS.
T286	192913-193065	Epistemic_statement	denotes	In conclusion, our results suggest that interaction of the Cag T4SS with phagocytic cells may contribute to immune evasion and persistence of H. pylori.
T287	193185-193387	Epistemic_statement	denotes	New 027 outbreak strains with global spreading are characterised by toxin A, B and binary toxin expression, mutations of a potential toxin repressor gene (tcdC), and increased toxin production in vitro.
T288	194433-194608	Epistemic_statement	denotes	Interestingly, the rate of various C. difficile genotypes was different between children and adults with high percentage of non-toxigenic strains in the pediatric group (50%).
T289	194609-194844	Epistemic_statement	denotes	Using an institutional database the genetic relationship between the various slpAST was analysed showing clustering in at least three major genetic groups subdivided in different subgroups with close association to known PCR ribotypes.
T290	194929-195016	Epistemic_statement	denotes	We could show that 027 rates recently decrease in our previously high-prevalent region.
T291	195017-195138	Epistemic_statement	denotes	We hypothesize that the rates of epidemic strains and presumably also strain specific virulence may change over time e.g.
T292	195139-195201	Epistemic_statement	denotes	due to host adaptation and possibly also in different regions.
T293	195202-195277	Epistemic_statement	denotes	Emergence of new epidemic C. difficile strains may occur at any time again.
T294	195429-195569	Epistemic_statement	denotes	SlpAST is a well standardized method to identify current epidemic C. difficile strains but also strains of still unknown epidemic relevance.
T295	195853-196012	Epistemic_statement	denotes	This protein translocation results in altered host cell gene expression profiles and cytoskeletal rearrangements, and it has been linked to cancer development.
T296	196191-196381	Epistemic_statement	denotes	Recently, it has been shown that the Cag type IV secretion apparatus binds to integrin molecules as receptors on host cells, and that several Cag components are involved in this interaction.
T297	196479-196722	Epistemic_statement	denotes	Previous studies have identified the cagI gene as an essential gene for translocation of CagA into host cells, but there have been conflicting results as to its requirement for stimulation of interleukin-8 (IL-8) secretion by epithelial cells.
T298	196723-196976	Epistemic_statement	denotes	Since the cagI gene overlaps and is co-transcribed with the cagL gene encoding another integrin-interacting protein essential for Cag functionality, this discrepancy might be due to transcriptional effects of the resistance markers used for mutagenesis.
T299	197132-197324	Epistemic_statement	denotes	The absence of several components of the secretion apparatus has an impact on CagI and CagL protein levels, indicating that (partial) assembly of the apparatus is required for their stability.
T300	197524-197651	Epistemic_statement	denotes	Taken together, our results are consistent with the assumption that CagI and CagL form a complex at the bacterial cell surface.
T301	198251-198416	Epistemic_statement	denotes	This was thought to be associated with the emergence of a more virulent strain, Clostridium difficile PCR ribotype 027, which was first reported in Germany in 20007.
T302	199903-200033	Epistemic_statement	denotes	Hospital discharge diagnosis data for 2010 are not yet available (2009: 120.8 CDI diagnoses/100.000 discharged hospital patients).
T303	200328-200430	Epistemic_statement	denotes	Discussion: The continuing increase of CDI cases that peaked in 2010 shows the urgent need for action.
T304	200431-200481	Epistemic_statement	denotes	The nature of this increase is not yet understood.
T305	200482-200540	Epistemic_statement	denotes	An improved characterization of cases is therefore needed.
T306	200742-200786	Epistemic_statement	denotes	This will help to focus preventive measures.
T307	201902-202016	Epistemic_statement	denotes	Preliminary analysis of the data showed that the isolates can be grouped into approximately 50 distinct ribotypes.
T308	202166-202284	Epistemic_statement	denotes	Discussion: Analysis of a large number of c. difficile from an expansive urban area has not been described in Germany.
T309	202285-202620	Epistemic_statement	denotes	It is interesting to scrutinise such data as one may be able to determine if the increasing incidence of CDAD is perhaps, unlike the case in North Anmerica, not associated with a specific clonal spread and therby also determine if the change is perhaps due to changes in medical practice rather than a shift in the bacterial virulence.
T310	202621-202952	Epistemic_statement	denotes	Our results show that the vast majority of the isolates possesed both toxin A and B genes and that only few [12.6 the binary toxin gene, a disproportionate number of these [60.6 %] however were located in isolates positive for tcdA and negative for tcdB genes, which only accounted for 7.8 % of the total number of isolates tested.
T311	203499-203573	Epistemic_statement	denotes	Thus, giardiasis is a major public and veterinary health concern globally.
T312	203574-203673	Epistemic_statement	denotes	It remains unclear to what degree it is a zoonosis and what determines its pathogenicity to humans.
T313	203674-203865	Epistemic_statement	denotes	To assess these issues a Gd biobank shall be generated to link epidemiological data with functional characteristics of clinical isolates and as a means to identify virulence associated genes.
T314	203866-204029	Epistemic_statement	denotes	We hypothesize that potential virulence markers are enzymes released by Giardia upon colonization of the small instestine and interaction with the host epithelium.
T315	204030-204285	Epistemic_statement	denotes	Especially the Gd arginine deiminase (ADI) that converts arginine to citrulline and ammonia shall be investigated as possible virulence and pathogenicity factor of Gd, because arginine plays a critical role in antimicrobial mechanisms and immune response.
T316	204286-204508	Epistemic_statement	denotes	The sequencevariation of ADI will be determined by cloning adi from Gd isolates being collected in the biobank and sequence variants will be functionally characterized by expressing the respective recombinant ADI proteins.
T317	204509-204652	Epistemic_statement	denotes	Finally, correlation between enzyme function and clinical pathology shall be investigated on basis of Gd isolates related epidemiological data.
T318	204653-204704	Epistemic_statement	denotes	We will present the establishment of this workflow.
T319	206911-207081	Epistemic_statement	denotes	Using a murine infection model we discovered distinct correlations between the metabolism of the tested amino acids and the persistence of C. jejuni in different tissues.
T320	207219-207362	Epistemic_statement	denotes	Gaussia princeps luciferase (Gluc) can be used to monitor type I protein secretion in Salmonella enterica serovar Typhimurium T. Wille 1 , R.G.
T321	207606-207671	Epistemic_statement	denotes	Data about the applicability of Gluc in bacteria is very limited.
T322	207672-207817	Epistemic_statement	denotes	Given the small size, high activity and co-factor independence of Gluc, it might be especially suited to monitor secretion of bacterial proteins.
T323	208581-208741	Epistemic_statement	denotes	We could show that a C-terminal moiety of SiiE including immunoglobulin (Ig) domain 53 is essential and sufficient mediating type I-dependent secretion of Gluc.
T324	208847-208929	Epistemic_statement	denotes	Discussion: In conclusion, Gluc can be used to monitor protein secretion via T1SS.
T325	209243-209417	Epistemic_statement	denotes	Helicobacter pylori BCS 100 genome variability and potential virulence determinants during an experimental human infection L. Kennemann* 1 , T. Aebischer 2 , S. Kuhn 1 , T.F.
T326	209819-209932	Epistemic_statement	denotes	Much less is known about genomic adaptations that may occur in the first months of infection of a new human host.
T327	209933-210210	Epistemic_statement	denotes	Here, we present the complete genome sequence of H. pylori strain BCS 100 (H1), a cagPAI deficient isolate that has been used for several human challenge studies in the US and Germany, and draft sequences of reisolates obtained from four volunteers after 3 months of infection.
T328	210211-210361	Epistemic_statement	denotes	Results: The genome sequence of H. pylori challenge strain H1 was obtained by 454 sequencing and subsequent gap closure by targeted Sanger sequencing.
T329	210984-211200	Epistemic_statement	denotes	Unexpectedly, a previously unknown variant of the input strain was detected in several volunteers which differed from the 454 sequenced input clone H1 by 86 SNPs and three clusters of nucleotide polymorphisms (CNPs).
T330	211201-211368	Epistemic_statement	denotes	This variant was commonly detected among the additional reisolates from the study, suggesting strong in vivo selection favoring this subpopulation in some human hosts.
T331	212616-212808	Epistemic_statement	denotes	We attempt to localize the distinct binding regions of these proteins within the receptor and we want to determine, whether binding of CagA to ITGB1 is an essential step in CagA translocation.
T332	212999-213196	Epistemic_statement	denotes	These data can help to propose a new model of interaction between the pathogenic H. pylori and the eukaryotic cell, mediated by specific interactions of the cag-T4SS and the ITGB1 of the host cell.
T333	213615-213747	Epistemic_statement	denotes	ACI outbreak specific findings included an association to university hospitals, to intensive care units, and to surgery departments.
T334	213748-213902	Epistemic_statement	denotes	PAE outbreaks were associated with significantly less use of isolation precautions, less frequently closure of wards, and less use of protective clothing.
T335	214572-214694	Epistemic_statement	denotes	However, from our point of view currently there is no MRGN bacterium that should be totally disregarded with this respect.
T336	214695-214891	Epistemic_statement	denotes	Essen, Deutschland 3 University Hospital Essen, Hospital Hygiene, Essen, Deutschland Introduction: Postoperative wound infections generally cause considerable extra morbidity, mortality and costs.
T337	216511-216642	Epistemic_statement	denotes	Attention should be paid to antibiotic prophylaxis and Methicillin-resistant Staphylococcus aureus (MRSA) nasal carriage treatment.
T338	216643-216733	Epistemic_statement	denotes	In this study BMI >30 and high blood-glucose levels were associated with wound infections.
T339	216734-216803	Epistemic_statement	denotes	Overall the rate of SSIs was low, but further surveillance is needed.
T340	217015-217176	Epistemic_statement	denotes	Mikrobiologie u.Krankenhaushygiene, Hannover, Deutschland Background: Hand hygiene is the most effective measure for preventing infections related to healthcare.
T341	217177-217510	Epistemic_statement	denotes	This study aims to evaluate the hand hygiene compliance in a German university hospital overall and in addiction to the professional status after implementation of the national hand hygiene campaign "Aktion Saubere Hände in 2008.This is the largest nationwide survey on intensive care units (ICU) in a university hospital in Germany.
T342	218412-218511	Epistemic_statement	denotes	No significant correlation between hand rub consumption and hand hygiene compliance was calculated.
T343	219579-219824	Epistemic_statement	denotes	Effective and rapid analysis of nosocomial outbreaks using the DiversiLab semi-automated repetitive sequence-based PCR test system Objectives: Rapid and sensitive methods are essential for typing and monitoring of hospital associated infections.
T344	219963-220252	Epistemic_statement	denotes	Aim of the study was to evaluate the usefulness and accuracy of the DiversiLab system for bacterial strain typing and determination of genetic relatedness of strains associated with nosocomial outbreaks and integration of the system in the workflow of a routine microbiological laboratory.
T345	220830-221017	Epistemic_statement	denotes	The same result could be observed in the 26 multi-resistant A. baumannii strains, where strains showed identical cluster formation (into 3 separate clusters) and very similar dendrograms.
T346	221967-222130	Epistemic_statement	denotes	-Results on the DiversiLab system could be obtained in a short period (8-24h), which is an essential advantage in rapid analysis of hospital associated infections.
T347	222380-222496	Epistemic_statement	denotes	However, often their actual ability of killing germs and their overall practicability in daily life remains unknown.
T348	222722-222861	Epistemic_statement	denotes	According to the manufacturer's instructions the wand should be used as close as possible and no more than one-half inch above the surface.
T349	222862-222978	Epistemic_statement	denotes	As stated in the operating manual, a 90% elimination of S. aureus would be expected within 12 sec by this procedure.
T350	223969-224196	Epistemic_statement	denotes	However, when using such a device for disinfection purpose in daily life, one has to keep in mind that 20 sec UV-C light exposition time was necessary in order to properly disinfect a rather small surface area from enterococci.
T351	224290-224453	Epistemic_statement	denotes	So there might be few opportunities when such a device could be a useful tool, but it seems less helpful on larger exterior due to time necessary for disinfection.
T352	225028-225168	Epistemic_statement	denotes	Different factors can control the survival of enteric viruses in aquatic environments such as temperature, sunlight, pH, and organic matter.
T353	225169-225277	Epistemic_statement	denotes	However, little is known about the effect of the flow rate on the concentration of viruses in surface water.
T354	226391-226475	Epistemic_statement	denotes	Moreover, no correlation between microbiological parameters and flow rate was found.
T355	226476-226590	Epistemic_statement	denotes	Further investigations are needed to characterize hydrological factors influencing enteric viruses in river water.
T356	226812-227217	Epistemic_statement	denotes	Homogeneous distribution of phenotypic characteristics in clonally unrelated Pseudomonas aeruginosa isolates from technical water systems H. Petry-Hansen* 1 , J. Hanke 1 , J. Heise 1 , H.-C. Flemming 1 , J. Wingender Biofilm Centre, Abteilung Aquatische Mikrobiologie, Essen, Deutschland P. aeruginosa is an opportunistic pathogen ubiquitously found in water environments where it can persist in biofilms.
T357	227218-227372	Epistemic_statement	denotes	Cells released from biofilms contaminate the water phase and pose a potential threat to human health, especially when occurring in man-made water systems.
T358	227373-227469	Epistemic_statement	denotes	The genotypic and phenotypic variability of P. aeruginosa in technical water systems is unknown.
T359	227871-228255	Epistemic_statement	denotes	For 77 representative strains and all seven reference strains the following characteristics were analyzed in order to reveal possible correlations between water source and genotypic as well as phenotypic characteristics: colony morphology, pigment production, hemolysis, cell surface hydrophobicity, biofilm formation, resistance against antibiotics and occurrence of virulence genes.
T360	229336-229470	Epistemic_statement	denotes	No correlation between phenotypic and genotypic traits, and between these characteristics and the origin of the strains were detected.
T361	229671-229791	Epistemic_statement	denotes	There seem to be no selection of a specific genotypic or phenotypic variant of P. aeruginosa in technical water systems.
T362	230116-230195	Epistemic_statement	denotes	Knowledge about the real frequency of nosocomial infections in Germany is rare.
T363	230854-230921	Epistemic_statement	denotes	Results: Overall, 1,047 in-patients could be included in the study.
T364	232380-232550	Epistemic_statement	denotes	Thorax-, Transplantationsund Gefäßchirurgie, Hannover, Deutschland Background: Hand hygiene is the most effective measure for preventing infections related to healthcare.
T365	232551-232700	Epistemic_statement	denotes	This study aims to evaluate the hand hygiene behaviour of health care workers in a German university hospital in treatment of special patient groups.
T366	232886-233043	Epistemic_statement	denotes	They are high risk patients for developing healthcare associated infections due to the high number of devices, the long hospital stays and immunosuppression.
T367	234647-234792	Epistemic_statement	denotes	Once the number of infected persons including hospital staff climbs to a threshold hospital departments may be closed or even the whole hospital.
T368	234793-235004	Epistemic_statement	denotes	Medical and administrative staff members especially those responsible for hospital hygiene management and infection control have a need to know where infectious patients are situated or should be transferred to.
T369	235178-235320	Epistemic_statement	denotes	In case of an outbreak admission, discharge and transfer (ADT) operations can be monitored, controlled and analysed retrospectively over time.
T370	235532-235660	Epistemic_statement	denotes	The text code allows for displaying multiple infections and is likely to become the preferred standard of the hospital operator.
T371	235661-235762	Epistemic_statement	denotes	So far Norovirus, ESBL, MRSA, Clostriods and other infections can be differentiated in the dashboard.
T372	236758-237009	Epistemic_statement	denotes	PROHIBIT aims to analyse existing guidelines and practices to prevent healthcare associated infections (HAI) in Europe, to identify factors that influence compliance with best practices and to test the effectiveness of interventions of known efficacy.
T373	237997-238104	Epistemic_statement	denotes	Seven of the 16 guidelines rate the scientific level of supporting evidence and strength of recommendation.
T374	238105-238212	Epistemic_statement	denotes	All but one guideline explicitly recommend placing symptomatic patients in a single room whenever possible.
T375	238213-238302	Epistemic_statement	denotes	Cleaning or disinfection of frequently touched surfaces is recommended in all guidelines.
T376	238303-238463	Epistemic_statement	denotes	However, only 13 include specific recommendation about disinfectants; out of these 11 prefer chlorine based solutions as specified in the ECDC guidance of 2008.
T377	238464-238515	Epistemic_statement	denotes	There is variation in hand hygiene recommendations.
T378	238876-239007	Epistemic_statement	denotes	In the UK and Ireland public reporting of CDI rates of individual hospitals has been established since 2007 and 2008, respectively.
T379	239176-239264	Epistemic_statement	denotes	Furthermore, there is important variation in scope and detailing of the recommendations.
T380	239265-239355	Epistemic_statement	denotes	The majority of guidelines do not rate the scientific level or strength of recommendation.
T381	239687-239797	Epistemic_statement	denotes	However, some technical challenges have to be taken into consideration to assure a safe use of these products.
T382	239798-239880	Epistemic_statement	denotes	Recently, it has been shown, that active ingredients of surface disinfectants e.g.
T383	239881-240010	Epistemic_statement	denotes	quaternary ammonium compounds can adsorp to the fabrics of wipes and impair the efficacy of the disinfectants significantly (1) .
T384	240110-240206	Epistemic_statement	denotes	Therefore, it was our aim to develop an easy and reproducible test method for this product type.
T385	240315-240466	Epistemic_statement	denotes	OR-tiles according to DGHM (2) were used as test surfaces and a standardized technique for direct application of the soaked wipes has been established.
T386	240467-240679	Epistemic_statement	denotes	In addition, the amount of disinfectant applied to the surface has been investigated Results: Our results show that the suggested assay is suitable to test the practice like efficacy of disinfectant wipe systems.
T387	240848-241027	Epistemic_statement	denotes	There is a strong correlation between the amount of impregnation solution and the amount that can be transferred on the surface which is mandatory for the efficacy of the product.
T388	241028-241251	Epistemic_statement	denotes	We were able to show that the amount of disinfectant that can be transferred from a wipe onto a surface is significant lower than the amounts that are applied on the test carriers in the current published standards (2, 3) .
T389	241252-241389	Epistemic_statement	denotes	Discussion: Now, a reproducible and easy standard method is available that can be used to show the microbicidal efficacy of wipe systems.
T390	241390-241572	Epistemic_statement	denotes	The authors strongly recommend testing the microbicidal efficacy of the wipe systems before practical use and before introducing these systems in positive lists such as VAH and SFHH.
T391	241932-242178	Epistemic_statement	denotes	In May 2011, a large outbreak of an O104:H4 STEC strain (HUSEC 41) expressing an ESBL-positive phenotype occurred with a hot spot in Schleswig-Holstein leading to great challenges in the laboratory diagnosis and infection control in the hospital.
T392	243086-243178	Epistemic_statement	denotes	For all patients displaying symptoms of HUS, STEC ESBL infection could be confirmed (18/18).
T393	243269-243327	Epistemic_statement	denotes	No causative pathogen could be identified in 16 specimens.
T394	243791-243879	Epistemic_statement	denotes	Medical face masks were suggested only for procedures with potential aerosol production.
T395	244595-244789	Epistemic_statement	denotes	To avoid misdiagnosis potentially guiding false initial therapy or infection control measures rapid screening diagnostic methods are required and have been developed by specialized laboratories.
T396	244790-244993	Epistemic_statement	denotes	However, taking into account the inflation-like increasing number of newly suspected cases, the majority of laboratories has become overloaded, and the risk of delayed diagnosis increases proportionally.
T397	245219-245408	Epistemic_statement	denotes	Pathogens to be detected include Shiga-like Toxin producing E.coli, thus we assumed that also the novel variant which is Shigatoxin 1 negative but Shigatoxin 2 positive could be identified.
T398	246026-246141	Epistemic_statement	denotes	Patients can be monitored more closely by the clinicians and test results associated to the clinical course of HUS.
T399	246382-246458	Epistemic_statement	denotes	or Clostridium difficile can be administered the correct antibiotic therapy.
T400	246459-246767	Epistemic_statement	denotes	The Luminex technology is widely available and the assays procedure is rather simple with a total hands-on time of less than 5 hours and a sample capacity of up to 96 samples per run, the assays is suitable for high throughput analyses and thus will cover the peaks in the epidemiological outbreak situation.
T401	249068-249188	Epistemic_statement	denotes	The phenotype with all antimicrobials tested sensitive may indicate a community rather than a nosocomial primary source.
T402	249189-249334	Epistemic_statement	denotes	We assume that after introduction of the strain -maybe by the family of the twins first affected -further nosocomial transmissions have occurred.
T403	249335-249372	Epistemic_statement	denotes	However, the parents were not tested.
T404	249707-249866	Epistemic_statement	denotes	Objective: To perform a prospective in-hospital surveillance of salmonella infection in order to detect possible nosocomial cases in an acute hospital setting.
T405	249867-250063	Epistemic_statement	denotes	Methods: In three tertiary care hospitals all patients with detection of salmonella species were investigated in respect to whether the detection occurred later than 48 h after hospital admission.
T406	251164-251259	Epistemic_statement	denotes	Conclusion: A systematic surveillance of all salmonella-cases identified rare nosocomial cases.
T407	251260-251374	Epistemic_statement	denotes	Food available at food providers near the hospital should be considered if nosocomial salmonella infection occurs.
T408	251618-251732	Epistemic_statement	denotes	Objective: Human Adenovirus (HAdV) can cause severe infections especially in haemato-oncologic pediatric patients.
T409	251733-251836	Epistemic_statement	denotes	In our hospital contactand droplet-precautions are recommended when infections with HAdV are suspected.
T410	251837-252026	Epistemic_statement	denotes	Despite this recommendation HAdV was identified in stool and nasopharyngeal secretion samples of five children in a pediatric haematooncology ward within a two week period in February 2010.
T411	252093-252238	Epistemic_statement	denotes	As a high compliance with precautions in ward staff was observed, the theory of an outbreak with patient to patient transmissions was questioned.
T412	253412-253551	Epistemic_statement	denotes	Possible reasons for the observed cluster may be transmission from parents or siblings or the reactivation of HAdV under immunosuppression.
T413	253552-253678	Epistemic_statement	denotes	Improved education and information of parents and other family members might be a useful additional effort in pediatric wards.
T414	253679-253818	Epistemic_statement	denotes	Objectives: The role of infected and/or colonized health care workers (HCWs) as a potential source of a nosocomial outbreak is yet unclear.
T415	253819-253971	Epistemic_statement	denotes	The present study summarizes data from such outbreaks in order to elucidate areas of special interest and to clarify potential reasons for transmission.
T416	255788-255913	Epistemic_statement	denotes	Conclusion: Nosocomial outbreaks caused by staff are an important problem in the field of epidemiology and infection control.
T417	255914-256038	Epistemic_statement	denotes	In the next step we will check for characteristics of HCWs that may predispose for an increased pathogen spread to patients.
T418	256551-256657	Epistemic_statement	denotes	We propose that humoral memory, acquired during colonization, shapes the response to S. aureus bacteremia.
T419	257313-257369	Epistemic_statement	denotes	This observation may be exploited for earlier diagnosis.
T420	258186-258332	Epistemic_statement	denotes	Interestingly, the clinical isolates inducing furunculosis frequently harbour the pvl-genes, encoding the toxin Panton-Valentine-Leukocidin (PVL).
T421	258660-258832	Epistemic_statement	denotes	To test whether invasive S. aureus strains that cause chronic furunculosis differ from colonizing strains we investigated their ability to induce cell death in neutrophils.
T422	259748-259829	Epistemic_statement	denotes	We can exclude indirect effects by modulating cytokines of contaminating T cells.
T423	260038-260147	Epistemic_statement	denotes	However, there were no differences between S. aureus cells from colonizing or furunculosis inducing isolates.
T424	260773-260829	Epistemic_statement	denotes	Schmidt 1 1 ZMBE, Infektiologie, Münster, Deutschland 2
T425	260830-260954	Epistemic_statement	denotes	Cell-penetrating proteins (CPP) are able to cross cellular membranes, either alone or in association with a bioactive cargo.
T426	261910-261982	Epistemic_statement	denotes	Free YopM could be detected throughout the cytoplasm and in the nucleus.
T427	262742-262768	Epistemic_statement	denotes	Horn 2 , M. Lindemann 2 1
T428	262769-262963	Epistemic_statement	denotes	Introduction: Vaccination against Streptococcus pneumoniae is recommended by the German advisory board for vaccination (STIKO) in immunocompromized patients such as kidney transplant recipients.
T429	262964-263065	Epistemic_statement	denotes	S. pneumoniae mainly infects the upper respiratory tract; it can cause lobar pneumonia or meningitis.
T430	263140-263276	Epistemic_statement	denotes	It was the aim of the present study to define the long-term efficiency of vaccination in clinically stable kidney transplant recipients.
T431	264489-264651	Epistemic_statement	denotes	Conclusion: Our results demonstrate that kidney transplant recipients can produce almost normal concentrations of antibodies against pneumococcal polysaccharides.
T432	265380-265531	Epistemic_statement	denotes	However, the activation of CD95 further increases pulmonary ceramide levelsand results in a vicious cycle of CD95 activation and ceramide accumulation.
T433	265852-266016	Epistemic_statement	denotes	These findings identify CD95 as an important regulator of lung functionsin cystic fibrosis and suggest that CD95 may be a novel target for treating cystic fibrosis.
T434	266305-266394	Epistemic_statement	denotes	The adaptive immune system can mobilize different effector mechanisms to a given antigen.
T435	269305-269396	Epistemic_statement	denotes	It appears that the cleavage of MyD88 uncouples the activation of TLR4 from NF-B signaling.
T436	269397-269528	Epistemic_statement	denotes	Thus, the disruption of MyD88 signaling in the execution of apoptosis may render the dying cells less sensitive to TLR stimulation.
T437	269529-269704	Epistemic_statement	denotes	This suggests that the cleavage of MyD88 is implicated in apoptotic death signaling by conferring immunogenic tolerance to the dying cell in response to microbial stimulation.
T438	269874-270002	Epistemic_statement	denotes	A crucial step in host colonization is the adhesin-mediated binding of this pathogen to the cells of the respiratory epithelium.
T439	270003-270199	Epistemic_statement	denotes	For cytadherence M. pneumoniae exhibits a complex membrane extension called attachment organelle which includes amongst other proteins the major adhesin P1 and the adherenceassociated protein P30.
T440	270887-271075	Epistemic_statement	denotes	We used this chimeric protein as antigen for an immunization strategy to elicit an antibody response in the respiratory tract of guinea pigs which can reduce the adhesion of M. pneumoniae.
T441	271737-271998	Epistemic_statement	denotes	The results are promising to achieve increased levels of M. pneumoniae-specific secretory IgA in comparison to the conventional systemic immunization by using the advantages of chitosan for the nasal vaccination of host organisms with the characterized antigen.
T442	272711-272793	Epistemic_statement	denotes	Two fibrinogen binding adhesins have been previously described for S. lugdunensis.
T443	272963-273043	Epistemic_statement	denotes	To date a fibronectin binding protein for S. lugdunensis has not been described.
T444	273044-273236	Epistemic_statement	denotes	We sought to investigate whether S. lugdunensis is internalized into the epithelial and endothelial cell line cells (5637 and EA.hy 926) using a previously described FACS-based invasion assay.
T445	273237-273402	Epistemic_statement	denotes	We could show that clinical isolates of S. lugdunensis were internalized into human urinary bladder carcinoma cell line 5637 and the endothelial cell line EA.hy 926.
T446	273403-273515	Epistemic_statement	denotes	Interestingly, all strains that invade into human urinary bladder carcinoma cell line 5637 bound to fibronectin.
T447	273800-274020	Epistemic_statement	denotes	The discovery of the internalization attribute of S. lugdunensis and its linkage to fibronectin binding suggests that the internalization of this important pathogen also occurs via a fibronectin mediated surface contact.
T448	274021-274293	Epistemic_statement	denotes	J. Elias* 1 , A. Tremmel 1 , U. Vogel 1 1 Universität Würzburg, Institut für Hygiene und Mikrobiologie, Würzburg, Deutschland Laboratory staff working with Neisseria meningitidis should be offered immunization with available vaccines against serogroups A, C, W-135, and Y.
T449	274294-274690	Epistemic_statement	denotes	As part of our biological safety management we have performed a crosssectional study with 20 individuals between 18 and 50 years, who were vaccinated once with quadrivalent polysaccharide vaccine; the aims of the study were: estimation of the duration of protection by polysaccharide vaccine; and assessment whether revaccination with newly available quadrivalent conjugate vaccine was necessary.
T450	275506-275580	Epistemic_statement	denotes	Mean protective duration, however, exceeded 100 months for all serogroups.
T451	275737-275864	Epistemic_statement	denotes	In conclusion, our analyses might point to less effective immunization against serogroup W135 by a polysaccharide-only vaccine.
T452	277143-277238	Epistemic_statement	denotes	The zymogen plasminogen can be converted by specific activators to the serine protease plasmin.
T453	278608-278794	Epistemic_statement	denotes	A20, an ubiquitin-editing enzyme, can block the proximal NF-B signalling pathway under various stimulations and A20 knockout mice succumb prematurely from uncontrolled hyperinflammation.
T454	280174-280314	Epistemic_statement	denotes	Interestingly, mRNA levels of iNOS, which is responsible for producing anti-malarial NO, were also significantly higher in infected KO mice.
T455	280315-280508	Epistemic_statement	denotes	Our study demonstrates that A20 deletion in hepatocytes is beneficial for parasite clearance during malaria liver stage infection, presumably by inducing a stronger local inflammatory response.
T456	280509-280616	Epistemic_statement	denotes	Augmenting anti-liver stage defense mechanisms may further improve experimental malaria vaccine strategies.
T457	281020-281100	Epistemic_statement	denotes	It has been shown that Mycobacteria infect their host by various mechanisms, eg.
T458	281224-281453	Epistemic_statement	denotes	Our group has found a lipid (Phenolic glycolipid, PGL) in the outer cell wall of Mycobacterium marinum (Mmar, a model organism for the research of Mtb) which might interfere with the innate immune system (Robinson et al., 2008) .
T459	281454-281561	Epistemic_statement	denotes	We are currently focused on establishing the link between PGL and the pathways of the innate immune system.
T460	282755-282881	Epistemic_statement	denotes	Discussion: Our findings suggest that PGL is indeed able to interfere with the signaling pathways of the innate immune system.
T461	282882-283007	Epistemic_statement	denotes	We could show that PGL supresses the production of IL-6, IL-12p40 and TNF-a RNA in HMDM after stimulation with HK-BCG or LPS.
T462	283129-283203	Epistemic_statement	denotes	It still remains elusive where exactly PGL interferes with these pathways.
T463	283320-283418	Epistemic_statement	denotes	Our work could therefore help to complete the picture of the infection mechanisms of Mycobacteria.
T464	283419-283559	Epistemic_statement	denotes	The intracellular protozoan parasite Toxoplasma gondii can invade the brain and cause a persistent infection, toxoplasmic encephalitis (TE).
T465	283560-283697	Epistemic_statement	denotes	IFNproducing CD8 + T cells, activated microglia, macrophages, and astrocytes appear to be the major effector mechanisms in host immunity.
T466	284099-284153	Epistemic_statement	denotes	Little is known about the role of ADAP in brain cells.
T467	284154-284369	Epistemic_statement	denotes	Since we could demonstrate that ADAP-deficient (ADAP -/-) mice showed ameliorated disease progression in the experimental autoimmune encephalomyelitis (EAE) model, a function of ADAP in brain cells was hypothesized.
T468	284841-285019	Epistemic_statement	denotes	Although the number of IFN-producing lymphocytes was increased in the brains of ADAP -/mice, all ADAP -/mice died until 54 days post infection, while all wild-type mice survived.
T469	285129-285350	Epistemic_statement	denotes	These data indicate an important role of ADAP for the activation of microglia cells during toxoplasmosis, whereas the integrin-mediated migration of T cells through the blood-brain-barrier seems to be independent of ADAP.
T470	285616-285641	Epistemic_statement	denotes	Zipfel 1,2 , C. Skerka 1
T471	285642-285779	Epistemic_statement	denotes	Staphylococcus aureus is a human pathogen that lives as a human commensal but can also cause superficial and life-threatening infections.
T472	287505-287710	Epistemic_statement	denotes	Although IFN-l has been shown to predominantly act on mucosal organs such as the lung and gastrointestinal tract, studies using IFN-l receptor-deficient mice have failed to define a non-redundant function.
T473	288087-288344	Epistemic_statement	denotes	Quantitative RT-PCR and simultaneous immunostaining of virus-infected cells and the antiviral Mx1 protein highlighted the distinct responsiveness of intestinal epithelial cells to IFN-l and its critical role to restrict epithelial viral replication in vivo.
T474	288684-288837	Epistemic_statement	denotes	This defence mechanism works very efficiently despite the often low number of pathogens and the limited amount of mediators secreted per epithelial cell.
T475	289167-289365	Epistemic_statement	denotes	Cell-to-cell communication was independent of gap junction formation, cytokine secretion, ion fluxes or nitric oxide synthesis, but required NADPH oxidase (Nox) 4-dependent oxygen radical formation.
T476	290011-290125	Epistemic_statement	denotes	However, tryptophan metabolites produced in the kynurenine pathway are able to inhibit the growth of immune cells.
T477	290643-290774	Epistemic_statement	denotes	Detailed analyses indicate that this antiparasitic effect is due to a toxic effect of the tryptophan metabolites on the host cells.
T478	291108-291182	Epistemic_statement	denotes	Quantitative analysis of the toxicity indicates that some tumor cells e.g.
T479	291369-291585	Epistemic_statement	denotes	These metabolites might inhibit the activity of tumor specific T-cells, while the enhanced resistance of some tumor cells against the toxic effect of tryptophan metabolites might represent an immune escape mechanism.
T480	291586-291769	Epistemic_statement	denotes	Background: Fibroblasts regulate epithelial cell differentiation, are responsible for wound healing, control inflammation process and seem to play an important role in cancerogenesis.
T481	291914-291966	Epistemic_statement	denotes	The linkage might be the hyaluronan (HA) metabolism.
T482	291967-292109	Epistemic_statement	denotes	Bacteria produce hyaluronidases and bacterial products interact with Toll-like-receptors (TLRs) which also seem to be linked to HA metabolism.
T483	292110-292250	Epistemic_statement	denotes	We investigated how far microorganisms/microbial products influence the metabolism of HA in human dermal fibroblasts through TLR activation.
T484	293475-293573	Epistemic_statement	denotes	However, all microorganisms and the microbial products under study did not modulate HA metabolism.
T485	293835-293933	Epistemic_statement	denotes	However, a possible role of HA metabolism in host-microorganism interacting needs further studies.
T486	294738-294898	Epistemic_statement	denotes	As to date, a constitutive expressed specific unique marker for human Treg cells is not available, an exact quantification on protein or RNA level is imprecise.
T487	295964-296064	Epistemic_statement	denotes	Heterologous antigens can be expressed in Salmonella as fusions with recombinant or native proteins.
T488	296065-296311	Epistemic_statement	denotes	This approach has been used mainly to direct the expression of the desired antigen to a particular location of the bacterial cell and to increase the immunogenicity of foreign antigens by fusing them to proteins that could exert a carrier effect.
T489	296312-296522	Epistemic_statement	denotes	The type III secretion system (T3SS)-mediated translocation by Salmonella can be used for efficient delivery of heterologous antigens into the cytosol of APC, leading to stimulation of both CD4 and CD8 T-cells.
T490	296649-296734	Epistemic_statement	denotes	These effectors proteins are associated with endosomal membranes after translocation.
T491	297136-297414	Epistemic_statement	denotes	By comparison of various attenuated carrier strains, we observed that the htrA/purD double mutant strain can be used efficiently as attenuated carrier for vaccination and observed the efficient stimulation invitro T-cell proliferation by the delta sifA mutant strain as carrier.
T492	297642-297810	Epistemic_statement	denotes	Differential expression and inducibility of Dusp gene expression suggest that these phosphatases specify the outcome of MAPK activation in terms of cytokine production.
T493	298411-298546	Epistemic_statement	denotes	However, embryonic development of homozygous mice was grossly normal until E18.5, indicating that Dusp16trap/trap mice die perinatally.
T494	299359-299490	Epistemic_statement	denotes	The cellular response of human monocyte derived macrophages to infection with genetically distinct M. tuberculosis complex strains
T495	299491-299754	Epistemic_statement	denotes	Aim of the study: The Mycobacterium tuberculosis complex (MTBC) was initially regarded as a highly homogeneous population; however, recent data suggest the causative agents of tuberculosis are genetically and functionally more diverse than appreciated previously.
T496	299755-299877	Epistemic_statement	denotes	The impact of this natural variation on the virulence of the pathogen and clinical manifestations remains largely unknown.
T497	300757-300936	Epistemic_statement	denotes	However, additional data also demonstrate that a particular MTBC genotype translates into a distinct biological response profile when getting into contact with human immune cells.
T498	301693-301786	Epistemic_statement	denotes	Nuclear localization was due to a so far unknown bipartite nuclear localization signal (NLS).
T499	302529-302627	Epistemic_statement	denotes	Limitation of p65 availability resulted in reduced expression of a subset of NFkB dependent genes.
T500	303597-303734	Epistemic_statement	denotes	How these unique transcriptional responses are generated, and which role they play for Th1 and Th17 induction is incompletely understood.

T1

Epistemic_statement

denotes

DVP01 "Inactivated mycobacteria bead preparation" method for identification of mycobacteria by MALDI-TOF MS DVP02 MALDI-TOF MS for functional detection of ß-lactam resistance of positive blood cultures DVP03 Molecular typing of Stenotrophomonas maltophilia from patients with cystic fibrosis by repetitive sequence-based PCR DVP04 Photochemical inactivation allows papid diagnostics of Alpha- and Poxviruses DVP05 Rapid detection and molecular differentiation of toxigenic Corynebacterium diphtheriae and Corynebacterium ulcerans strains by LightCycler PCR DVP06 Use of recombinant proteins for optimized serodiagnosis of M. pneumoniae infections DVP07 MALDI-TOF-MS analysis of bacteria difficult to identify by standard procedures DVP08 Carbapenemase detection by phenotypic methods DVP09 Direct identification of uropathogens by MALDI-TOF-MS and interfering factors DVP10 Comparison of different methods for the isolation of tick DNA

T2

946-1131

Epistemic_statement

denotes

Introduction: Next to the clinical important Mycobacterium tuberculosis complex (MTC) Nontuberculosis mycobacteria (NTM) are pathogens especially in immunocompromised and senior people.

T3

5911-6053

Epistemic_statement

denotes

Therefore, only the decrease of the molecular peak of Ertapenem can be employed as indicator for resistance against carbapenems at the moment.

T4

6054-6240

Epistemic_statement

denotes

Additional peaks appear in the spectra of the carbapenemase positive strains but these do not directly correspond to the hydrolyzed form of Ertapenem and have not been identified so far.

T5

7643-7772

Epistemic_statement

denotes

A small proportion of isolates were clonally related (12%), suggesting either cross-transmissions or a common source of exposure.

T6

8003-8289

Epistemic_statement

denotes

The objective of this study was to determine whether photochemical inactivation of viruses could be accomplished with high efficiency while preserving the molecular integrity of viral targets allowing subsequent diagnostic tests to be performed at a lower level of containment and cost.

T7

8993-9277

Epistemic_statement

denotes

The presented data could assist in developing methods to inactivate in the field environmental and forensic samples suspected of contamination with high virulence virus, thus limiting the need for costly security and safety operations after an accidental or intentional viral release.

T8

9786-9975

Epistemic_statement

denotes

Since the respective tox genes of C. diphtheriae and C. ulcerans differ in both DNA and amino acid sequence from each other, both tox genes should be covered by novel real-time PCR methods.

T9

10263-10539

Epistemic_statement

denotes

Background: Detection of Enterobacteriaceae carrying carbapenemases is challenging since the MIC can be in the susceptible range and because differentiation between carbapenem resistance due to carbapenemases or other mechanisms is not possible by routine susceptible testing.

T10

12027-12125

Epistemic_statement

denotes

Conclusions: In contrast to recommendations by CLSI the MHT should also be performed for imipenem.

T11

12126-12225

Epistemic_statement

denotes

Despite a lower specifity the importance of carbapenemase detection justifies a higher sensitivity.

T12

12226-12342

Epistemic_statement

denotes

Caution should be used in choosing the test media since huge differences in metallobetalactamase detection are seen.

T13

14024-14191

Epistemic_statement

denotes

These proteins are produced naturally in the body and cannot be removed simply by washing the filter residue because they closely interact with the bacterial membrane.

T14

14278-14385

Epistemic_statement

denotes

In ticks different pathogens can be found that may cause serious infections in humans and domestic animals.

T15

14628-14801

Epistemic_statement

denotes

Since the question regarding optimal DNA extraction from ticks is only poorly addressed so far, the present study compared different methods for isolation of DNA from ticks.

T16

17054-17211

Epistemic_statement

denotes

As minimal inhibitory concentration (MIC) of these strains can be increased but below the standard CLSI-breakpoints, further confirmatory tests are required.

T17

18320-18371

Epistemic_statement

denotes

By PCR 26 ESBL-positive E. coli could be confirmed.

T18

18898-18974

Epistemic_statement

denotes

However, use of disk diffusion tests is often more staff-and time-intensive.

T19

18975-19100

Epistemic_statement

denotes

Background: Enterobacteriaceae resistant to carbapenems are a growing problem in an increasing number of countries worldwide.

T20

19101-19230

Epistemic_statement

denotes

In Germany, carbapenemase resistance is still rare, but appears to be rising, and several hospital outbreaks have been described.

T21

20209-20360

Epistemic_statement

denotes

Random PCR (RAPD) was attempted to prove clonal origin of the isolates, yet, in case of these K. pneumoniae isolates the method was not discriminative.

T22

20361-20689

Epistemic_statement

denotes

As an alternative for rapid typing, MALDI-TOF spectra of isolates were compared yielding an excellent spectrum identity between outbreak strains and a good discrimination towards other unrelated isolates, yet, automated calculation of the dendrogram by the biotyper software was not applicable for intra-species differentiation.

T23

20849-20989

Epistemic_statement

denotes

RAPD), the diagnostic use of MALDI-TOF spectra may be helpful for preliminary epidemiologic analysis of clinical outbreaks within few hours.

T24

20990-21118

Epistemic_statement

denotes

The values and limitations of the method need to be further validated for different microorganisms by a standard procedure (e.g.

T25

21119-21268

Epistemic_statement

denotes

PFGE, MLST), yet, ease of applicability and low running costs make mass spectra analysis a promising tool for first line clinical outbreaks analysis.

T26

24572-24786

Epistemic_statement

denotes

We examined whether the analysis of bacterial protein patterns by MALDI-TOF-MS (Matrix-assisted laser desorption/ionization time of flight mass spectrometry) results in an unequivocal identification in those cases.

T27

24787-25109

Epistemic_statement

denotes

Methods: Isolates obtained from tissues and fluids of patients in the clinical routine which could not be unambiguously identified by API ® or VITEK ® or by gas chromatography, respectively, were analyzed by MALDI-TOF-MS. A small number of bacterial cells from the culture plate was directly deposited onto a sample plate.

T28

25483-25668

Epistemic_statement

denotes

Results: By using MALDI-TOF-MS analysis we could identify nearly 80 % of all isolates which previously had not given a clear result when standard identification procedures were applied.

T29

25669-25776

Epistemic_statement

denotes

In most cases the bacteria could be identified at the species level, in some cases only at the genus level.

T30

27296-27564

Epistemic_statement

denotes

Although, studies dealing with cost effectiveness of PCR in the management of CDAD patients are sparse, the BD GenOhm Cdiff assay (PCR) has greater analytical sensitivity than a conventional toxin ELISA maintaining comparable specificity in samples from CADA patients.

T31

27565-28021

Epistemic_statement

denotes

A. Halfmann* 1 , U. Geipel 1 , L. von Müller 1 , M. Herrmann 1 1 University Hospital of Saarland, Institute for Medical Microbiology and Hygiene, Homburg, Deutschland Background: Universal screening for methicillin-resistant Staphylococcus aureus (MRSA) is a valuable tool to estimate MRSA prevalence, yet, for a single institution, the laboratory challenges of a large campaign requiring quality-assured handling and processing of samples can be enormous.

T32

29380-29634

Epistemic_statement

denotes

Subsequently, several modifications on the WASP specimen processing protocol (various vortexing times, quantities of medium plated or streaking patterns) were carried out with support of the readily available WASP technical team both on-line and on-site.

T33

30902-31023

Epistemic_statement

denotes

Most people become infected with EBV at an early age, which is often asymptomatic but may cause infectious mononucleosis.

T34

31111-31265

Epistemic_statement

denotes

Although the symptoms of infectious mononucleosis usually resolve in 1 or 2 months, EBV dormant or latent in a few cells in the throat and blood for life.

T35

31266-31365

Epistemic_statement

denotes

Periodically, the virus can reactivate and is commonly found in the saliva of infected individuals.

T36

33308-33507

Epistemic_statement

denotes

Several studies have been published that claimed to identify oxacillin resistance of Staphylococcus aureus by whole cell matrix assisted laser desorption time of flight (MALDI-TOF) mass spectrometry.

T37

33652-33875

Epistemic_statement

denotes

Nevertheless, the study design in all of those studies was not suitable to achieve this goal, because only mecA/SCCmec isogenic strains could discriminate between strain specific-and mecA / SCCmec-dependent peak variations.

T38

34295-34375

Epistemic_statement

denotes

The loss of the mecA gene during freezing culture has been previously described.

T39

34656-34780

Epistemic_statement

denotes

In two out of 16 samples we could select a mecA containing strain and a corresponding isogenic strain lacking the mecA gene.

T40

35472-35724

Epistemic_statement

denotes

In contrast to several reports in literature, we could show for the first time that whole cell MALDI-TOF MS-derived peak profiles are not suitable for the discrimination of mecA positive S. aureus strains in the mass-to-chargeratio of 2000 to 15000 Da.

T41

36293-36403

Epistemic_statement

denotes

However, the resolution of complex mixtures, detection of antibiotic resistance markers are still unmet needs.

T42

36404-36662

Epistemic_statement

denotes

In order to overcome these limitations, a new molecular technology, PCR coupled to Mass Spectrometry, was developed, allowing detection and identification of multiple pathogens and selected antibiotic resistance markers or virulence factors in a single test.

T43

38474-38627

Epistemic_statement

denotes

Type II NADH dehydrogenases can occur either as internal enzymes, which utilize mitochondrial NADH, or as external enzymes, which utilize cytosolic NADH.

T44

38628-38849

Epistemic_statement

denotes

We determined the orientation of both isoforms by applying a split GFP complementation approach and could demonstrate that both isoforms are internal enzymes, which face with their active site to the mitochondrial matrix.

T45

39307-39524

Epistemic_statement

denotes

A functional complementation was possible by ectopic expression of the deleted gene, but not by expression of the heterologous isoform, suggesting that the two enzymes possess nonredundant, isotype-specific functions.

T46

41190-41326

Epistemic_statement

denotes

Additionally, no parasite-induced cell lysis could be observed in differentiated C2C12 in contrast to nondifferentiated C2C12 or NIH3T3.

T47

41620-41752

Epistemic_statement

denotes

Therefore, we also investigated whether MAPK might control T. gondii development in differentiated and undifferentiated C2C12 SkMCs.

T48

42187-42316

Epistemic_statement

denotes

Together, these results suggest that the host cell type and the differentiation of SkMCs regulate T. gondii replication in vitro.

T49

42317-42430

Epistemic_statement

denotes

This might also explain the different efficiencies of T. gondii to persist in differentiated tissues of the host.

T50

42431-43054

Epistemic_statement

denotes

The Candida albicans factor H binding molecule Hgt1p also functions as complement receptor 3 (CR3) and HIV binding molecule EKP07 Caenorhabditis elegans as a host model system to screen novel antifungal benzimidazole derivatives A. Singh* 1 , W. Abu Rayyan 1 , T. Dietsche 1 , H. Eickhoff 2 , K.-H. Wiesmüller 2 , K. Schröppel 1 1 Universitätsklinikum Tübingen, Interfakultäres Institut für Mikrobiologie und Infektionsmedizin, Tübingen, Deutschland 2 EMC microcollections GmbH , Tübingen, Deutschland Candida albicans, a commensal microorganism, is a causative agent of opportunistic oral and genital infections in humans.

T51

43130-43350

Epistemic_statement

denotes

Treatment of invasive fungal infections is problematic due to several persisting therapeutic drawbacks, in particular development of resistance against the currently available drugs or toxic side effects for the patient.

T52

43441-43596

Epistemic_statement

denotes

Previously, the nematode Caenorhabditis elegans has been successfully used as a model host for human pathogens and to screen for novel antimicrobial drugs.

T53

43597-43782

Epistemic_statement

denotes

It has been shown that C. albicans colonizes the intestinal tract of C. elegans and establishes a persistent lethal infection accompanied by deep tissue invasion of the entire organism.

T54

44760-44930

Epistemic_statement

denotes

During in vivo infection studies, we could demonstrate that EMC120B12 can inhibit filamentation of C. albicans and prolong survival of the C. albicans infected nematodes.

T55

44931-45181

Epistemic_statement

denotes

EMC120B12 identified in this screen can potentially be used as an effective antifungal agent and will be further investigated for its activity against other fungal species and also in a murine model to study its activity against systemic candidiasis.

T56

45581-45785

Epistemic_statement

denotes

However, these internal walls contain central pores allowing the exchange of molecules, nutrients and even organelles enabling the mycelium to respond as a functional entity to changes in the environment.

T57

45786-45907

Epistemic_statement

denotes

The draw-back of this organization is that a local damage of the cell wall is a potential threat for the whole syncytium.

T58

46060-46294

Epistemic_statement

denotes

In several fungi the Hex1 or HexA protein has been identified a major and essential component of the Woronin body and mutants generated in Neurospora crassa or Aspergillus oryzae show uncontrolled loss of cytoplasm after local damage.

T59

46295-46484

Epistemic_statement

denotes

Loss of Hex1 in Magnaporthe grisea impairs the virulence of this plant pathogen, but no data are yet available on the role of Hex proteins in filamentous fungi causing infections in humans.

T60

47483-47862

Epistemic_statement

denotes

Functional analysis of C. albicans infection-associated genes with unknown function during interaction with host cells and in complex infection models I. Jacobsen* 1 , D. Wilson 1 , F. Mayer 1 , B. Hube Mikrobielle Pathogenitätsmechanismen, Jena, Deutschland Introduction: Candida albicans is a common fungal pathogen in humans and able to cause a variety of clinical infections.

T61

47863-48050

Epistemic_statement

denotes

We hypothesized that C. albicans unknown function genes, which are transcriptionally upregulated during infection ("infection associated genes") might contribute to the infection process.

T62

48051-48165

Epistemic_statement

denotes

Aim and Methodology: We aimed to determine whether C. albicans infection associated genes contribute to virulence.

T63

48166-48374

Epistemic_statement

denotes

Therefore, based on transcriptional profiling from oral infections, liver invasion and incubation in human blood, we selected a subset of infection-associated genes with unknown function for further analysis.

T64

48375-48555

Epistemic_statement

denotes

Isogenic deletion mutants were constructed and subsequently tested in extensive in vitro screens, interaction with epithelial and endothelial cells and in complex infection models.

T65

48556-48708

Epistemic_statement

denotes

Results: Twentyfour isogenic deletion mutants were constructed and subsequently analyzed both in vitro and in infection models of increasing complexity.

T66

48965-49178

Epistemic_statement

denotes

To determine whether the deleted genes influenced virulence in more complex infections models, all 24 mutants were tested in ovo for their ability to kill chicken embryos infected on the chorio-allantoic membrane.

T67

49179-49359

Epistemic_statement

denotes

We recently showed that mortality in this model depends on the fungal ability to invade the membrane and that the pro-inflammatory host response likely contributes to pathogenesis.

T68

49360-49497

Epistemic_statement

denotes

Surprisingly, only seven mutants were attenuated in this model, of which five were also attenuated in damaging epithelial cells in vitro.

T69

49781-49993

Epistemic_statement

denotes

Discussion and Outlook: Our results demonstrate that genes essential for causing full damage of epithelial or endothelial cells in vitro are not necessarily crucial for full virulence in complex infection models.

T70

49994-50257

Epistemic_statement

denotes

We conclude that either such damage potential is not critical for full virulence in the complex host setting or that the greater complexity of the environment in animal models stimulates additional fungal regulatory networks leading to compensation of the defect.

T71

50258-50539

Epistemic_statement

denotes

Thiol-dependent redox networks: analysing the effects of the anti-malarial agent Methylene Blue Introduction: The development and spread of resistance against standard antimalarial drugs such as chloroquine (CQ) and pyrimethamine/sulfadoxin (PSD) has been a challenge for 25 years.

T72

52643-52759

Epistemic_statement

denotes

Conclusions: Taken together, our data suggest that MB could become a key factor in drug combination therapy efforts.

T73

52760-52834

Epistemic_statement

denotes

This should be tested more as a promising local eradication strategy [3] .

T74

54650-54797

Epistemic_statement

denotes

Interestingly, the tec1/tec1 phenotype was rescued in a mutant containing an ORF with an additional 72 aa that spanned the region from 1 to 709 aa.

T75

55555-55741

Epistemic_statement

denotes

Accumulating evidence indicates an involvement of RNA-binding proteins in regulating expression programmes underlying pathogenic development of the phytopathogenic fungi Ustilago maydis.

T76

56156-56313

Epistemic_statement

denotes

Khd4 recognizes a distinct hexanucleotide motif which is present in almost 25% of all annotated transcripts, suggesting a large regulatory potential of Khd4.

T77

56415-56478

Epistemic_statement

denotes

The precise role and function of Khd4 however is still unclear.

T78

57256-57345

Epistemic_statement

denotes

The high mortality of these infections is largely due to the limited therapeutic options.

T79

57346-57465

Epistemic_statement

denotes

Since A. fumigatus seems to lack sophisticated virulence traits, alternative therapeutic targets have to be identified.

T80

57555-57676

Epistemic_statement

denotes

Interference with signaling pathways helping the fungus to adapt to situations of stress is therefore a promising option.

T81

57677-57798

Epistemic_statement

denotes

However, this approach is hampered by the fact that many signaling pathways and molecules are conserved in fungi and men.

T82

58141-58236

Epistemic_statement

denotes

A similar protein architecture has recently been proposed to constitute an osmo-sensing module.

T83

58798-59059

Epistemic_statement

denotes

Mutants defective in genes of the cell wall integrity (CWI) pathway are significantly more sensitive to fludioxonil suggesting either a cross-talk between the HOG and the CWI pathway and/or a requirement for cell wall dynamics to bear fludioxonilinduced stress.

T84

60309-60441

Epistemic_statement

denotes

According to their homologues in S. cerevisiae, some of the genes deleted in mutants are presumably involved in cell wall integrity.

T85

60442-60631

Epistemic_statement

denotes

Since cell wall integrity is crucial for stress resistance and virulence, further analysis of deletion mutant strains which are predicted to be part of one signalling network was performed.

T86

61018-61223

Epistemic_statement

denotes

Similar behaviour could be observed while assaying cell wall stability and composition, with slg1 having considerably changed properties in comparison to the mutant strains mid2 and slt2 and the wild type.

T87

61224-61493

Epistemic_statement

denotes

Comparing the trancriptomes of the deletion strains with the wild type in the presence or absence of congo red showed only very slight changes in the expression pattern of mid2 and slt2, whereas in slg1 a significantly changed transcriptional profile could be detected.

T88

61494-61608

Epistemic_statement

denotes

The results obtained suggest that SLG1 has a different role in C. glabrata than in S. cerevisiae compared to MID2.

T89

61609-61741

Epistemic_statement

denotes

The function of the inspected genes of the cell wall integrity pathway in S. cerevisiae might therefore be different in C. glabrata.

T90

64333-64537

Epistemic_statement

denotes

Trypanosomal transmigration across the optimized ECV304-C6 model occurs in both directions underlining the possibility of a relapsing parasitemia after treatment with drugs that have no access to the CNS.

T91

64538-64711

Epistemic_statement

denotes

This model promotes the analysis of the cellular and molecular mechanisms underlying the CNS invasion, which is urgently needed for therapy improvement and drug development.

T92

65045-65225

Epistemic_statement

denotes

Tight junctional transmembrane proteins, notably claudins, regulate paracellular permeability of the intestinal barrier, constricting diffusion of small solutes and macromolecules.

T93

65226-65314

Epistemic_statement

denotes

Barrier function can be affected by pathogenic microorganisms, toxins and other stimuli.

T94

67440-67541

Epistemic_statement

denotes

Outlook: The results indicate an active participation of C. albicans in intestinal barrier breakdown.

T95

67542-67656

Epistemic_statement

denotes

However, the relative impacts of host and fungus on barrier disturbance will have to be clarified in ongoing work.

T96

68339-68604

Epistemic_statement

denotes

Immigrating immune cells are characterized by an increased glucose uptake, which can be used for non-invasive imaging: Fluorine labeled glucose (FDG -2-[ 18 F]fluoro-2-deoxy-D-glucose) is used as tracer for positron emission tomography/computer tomography (PET/CT).

T97

68605-68748

Epistemic_statement

denotes

Alternatively, a fluorescence labeled glucose derivative (RediJect 2-DG-750 Probe, Caliper) is detectable by the In-Vivo-Imaging-System (IVIS).

T98

68749-69064

Epistemic_statement

denotes

Since non invasive imaging tools to monitor inflammation have the potential to reduce the number of laboratory animals needed for the investigation of IA, we aimed to determine whether the above mentioned in vivo imaging systems are suitable for the quantification of the host's inflammatory response to IA in mice.

T99

71004-71310

Epistemic_statement

denotes

Zipfel 2 , C. Skerka 2 , G. Pradel 1 1 Research Center for Infectious Diseases, Würzburg, Deutschland 2 Leibniz Institute for Natural Product Research and Infection Biology, Jena, Deutschland As part of the innate immune system, the human complement is a first line of defence against microbial infections.

T100

72239-72376

Epistemic_statement

denotes

FH comprises 20 complement control protein modules, and binding of FH to malaria gametes appears to be primarily mediated by modules 1-7.

T101

72720-72812

Epistemic_statement

denotes

Our findings might lead to novel approaches in the design of transmission blocking vaccines.

T102

72813-72908

Epistemic_statement

denotes

Up to now there is only little data on the interaction of human NKC with the pathogenic fungus.

T103

72909-73013

Epistemic_statement

denotes

However, after NKC depletion mice have been shown to be more susceptible to systemic Candida infections.

T104

73014-73148

Epistemic_statement

denotes

On the basis of these observations we investigated if there are direct or indirect effects of human NK Cells against Candida albicans.

T105

74816-74945

Epistemic_statement

denotes

Blocking experiments suggest that the cytotoxic effect is perforin dependent while FasL/TRAIL receptor pathways are not involved.

T106

74946-75104

Epistemic_statement

denotes

In parallel to these direct effects, NKC may interact with other immune cells since cytokine release shows an upregulation of neutrophil activating cytokines.

T107

75105-75231

Epistemic_statement

denotes

Conclusions: Our observations suggest that NKC may play an important role in the first line defense of C. albicans infections.

T108

75232-75330

Epistemic_statement

denotes

In this context, direct and indirect antifungal effects of NKC are currently further investigated.

T109

75615-75773

Epistemic_statement

denotes

Although the incidence of fungal sepsis has increased recently, diagnosis is still difficult and mainly relies on the detection of the pathogen (Candida spp.)

T110

75955-76066

Epistemic_statement

denotes

These analyses will allow identifying immune markers which might be potentially useful in clinical diagnostics.

T111

76389-76501

Epistemic_statement

denotes

Further investigation included the characterisation of the whole blood transcriptome in response to C. albicans.

T112

76502-76653

Epistemic_statement

denotes

The obtained data will be integrated using bioinformatic methods to generate a network of innate immune activation during early steps of fungal sepsis.

T113

77018-77128

Epistemic_statement

denotes

As expected, myeloperoxidase from primary and lactoferrin from secondary granules could be detected in plasma.

T114

78046-78181

Epistemic_statement

denotes

Advantages over isolated primary cells are the physiological conditions and the possible communication between immune cell populations.

T115

78411-78460

Epistemic_statement

denotes

Protozoans like Leishmania can undergo apoptosis.

T116

78761-78914

Epistemic_statement

denotes

However, the protein machinery mediating apoptosis in mammalian cells like caspases or members of the bcl-2 families are completely absent in Leishmania.

T117

80365-80561

Epistemic_statement

denotes

In recent years, there has been increasing evidence for the occurrence of PCD in distinct unicellular organisms as well, however, there is only little information about putative PCD in Toxoplasma.

T118

80562-80690

Epistemic_statement

denotes

Therefore, identification of apoptosis-like markers and molecules that might play a role in T. gondii PCD need to be elucidated.

T119

82067-82207

Epistemic_statement

denotes

In order to unravel possible functions of T. gondii BI proteins in regulation of apoptosis, we heterologously expressed TgBIs in HeLa cells.

T120

82866-83012

Epistemic_statement

denotes

These findings suggest the existence of apoptotic-like cell death in T. gondii and protective effects of TgBI proteins in regulation of apoptosis.

T121

83410-83637

Epistemic_statement

denotes

Infection of individuals with premature or suppressed immunity can lead to lifethreatening toxoplasmosis whereas in immune competent hosts, infection is mostly asymptomatic but leads to parasite persistence for the host's life.

T122

83638-83758

Epistemic_statement

denotes

Cell-mediated immunity including the production of IFN-is critical for control of the obligatory intracellular parasite.

T123

83759-83968

Epistemic_statement

denotes

However, by using genomewide transcriptome analysis, we have shown that T. gondii leads to global unresponsiveness of murine macrophages to IFN-and this may be essential for establishing a long-term infection.

T124

85113-85306

Epistemic_statement

denotes

Together, these data unravel novel insights into the mechanisms by which T. gondii evades IFN-regulated immunity and open up novel strategies for therapeutic intervention against toxoplasmosis.

T125

86753-87163

Epistemic_statement

denotes

In biofilm assays, the full length TEC1 ORF was able to restore the ability for biofilm formation ability in the tec1/tec1 mutant background after Tet induced gene expression, and the biofilm mass was similar to the biofilm formed by the wild type SC5314 strain, whereas the TEA domain mutant and mutants lacking the proposed C-terminal motif were impaired in biofilm formation under similar growth conditions.

T126

87324-87555

Epistemic_statement

denotes

Further in vivo investigations with C. elegans infection model revealed that the C. albicans TEC1 mutant lacking this C-terminal motif shows less virulence against nematodes in terms of hyphal invasion and killing of the nematodes.

T127

87816-87985

Epistemic_statement

denotes

It can be demonstrated that this C-terminal motif of Tec1p is essential for yeast-hyphae transition, infection and killing of C. elegans nematodes and biofilm formation.

T128

88039-88263

Epistemic_statement

denotes

Scharf 1 1 Universitätsklinikum Düsseldorf, Institut für Hämostaseologie und Transfusionsmedizin, Düsseldorf, Deutschland Introduction: Candida albicans is a dimorphic fungus that can switch between the yeast and hypha form.

T129

88349-88408

Epistemic_statement

denotes

Platelets can bridge the innate with the adaptive immunity.

T130

88516-88654

Epistemic_statement

denotes

Platelet integrins and their plasma ligands can govern both binding to the pathogen and activation of platelets to release their granules.

T131

88655-88836

Epistemic_statement

denotes

Here we tested the hypothesis that fibronectin (which is also stored in platelet -granular and bound by platelet integrins) supports the host defense against C. albicans infections.

T132

90319-90484

Epistemic_statement

denotes

Hence, platelets and fibronectin, with its intrinsic multivalent binding site can support the platelet mediated host defense and immune response against C. albicans.

T133

90835-91298

Epistemic_statement

denotes

Its central MAP kinase module was subject of diverse studies and is conserved from Saccharomyces cerevisiae to filamentous fungi, such as Aspergillus spp.. On the contrary, components upstream of this MAP kinase module are well characterized in S. cerevisiae but largely unknown in Aspergillus spp.. We have identified, localized and functionally characterized homologues of the S. cerevisiae cell surface sensors ScWsc1 -ScWsc3 and ScMid2/ScMtl1 in A. fumigatus.

T134

91551-91691

Epistemic_statement

denotes

In addition, our data indicate fundamental functional differences on the sensor level of the CWI pathways of S. cerevisiae and A. fumigatus.

T135

91692-92176

Epistemic_statement

denotes

Trends in multidrug resistance among Escherichia coli and klebsiellae in Germany M. Kresken* 1,2 , D. Hafner 2,3 1 Antiinfectives Intelligence GmbH, Rheinbach, Deutschland 2 Paul-Ehrlich-Gesellschaft für Chemotherapie e.V., Rheinbach, Deutschland 3 Institute for Pharmacology and Clinical Pharmacology, Heinrich-Heine-University, Düsseldorf, Deutschland Introduction: Escherichia coli (ECO) and klebsiellae are among the most common pathogens causing infections in in-and outpatients.

T136

92177-92334

Epistemic_statement

denotes

Antimicrobial agents such as 3rd generation cephalosporins (3GC), carbapenems (carba) and fluoroquinolones (FQ) are essential drugs to treat serious illness.

T137

92335-92499

Epistemic_statement

denotes

Treatment outcome, however, has increasingly been threatened by the emergence and dissemination of resistant (R) strains (multi-drug R [MDR] strains in particular).

T138

99328-99502

Epistemic_statement

denotes

pathogens in Germany, all clinically used dosing regimens of CARBA are sufficient to achieve a probability of 95% or greater success against CRO-resistant Enterobacteriaceae.

T139

101794-101897

Epistemic_statement

denotes

However, there was an alarming increase of ESBL rates in outpatients from 1.3% in 2007 to 5.9% in 2010.

T140

102066-102126

Epistemic_statement

denotes

Probably the outbreak was caused by contaminated vegetables.

T141

103068-103165

Epistemic_statement

denotes

The isolated displayed an ESBL phenotype and blaTEM-1 as well as blaCTX-M-15 could be identified.

T142

103548-103635

Epistemic_statement

denotes

No co-resistance to tetracycline or sulfamethoxazoletrimethoprim could be demonstrated.

T143

103636-103838

Epistemic_statement

denotes

Conclusion: Within two days after receipt of the EHEC outbreak isolate the molecular basis of its unusual ESBL phenotype could be clarified and was immediately reported to the German health authorities.

T144

103905-104096

Epistemic_statement

denotes

The presence of resistance genes in diarrheagenic bacterial strains is worrisome since it might contribute to an enhanced spread of resistance determinants, e. g. by horizontal gene transfer.

T145

104371-104473

Epistemic_statement

denotes

Data on the in vitro susceptibility of pathogens isolated from ocular infections, however, are scarce.

T146

106823-106975

Epistemic_statement

denotes

Carbapenem resistance in P. aeruginosa can be caused by a variety of mechanisms, however the worldwide spread of carbapenemases is especially important.

T147

108347-108461

Epistemic_statement

denotes

An unspecific result due to toxicity of EDTA could be excluded by a positive bioassay based on cell-free extracts.

T148

108861-109010

Epistemic_statement

denotes

It clearly shows a MBL phenotype, while the MIC differences for imipenem are likely to be the result of additional mechanism for imipenem resistence.

T149

109802-109906

Epistemic_statement

denotes

However, the correct identification of carbapenemases is challenging for the microbiological laboratory.

T150

110177-110266

Epistemic_statement

denotes

A bioassay based on cell-free extracts allows the detection of still unknown -lactamases.

T151

110517-110833

Epistemic_statement

denotes

Several different carbapenemases could be detected, including OXA-48 (n = 59), KPC-2 (n = 31), KPC-3 (n = 26), VIM-1 (n = 37), VIM-2 (n = 20), VIM-4 (n = 4), VIM-5 (n = 1), IMP-7 (n = 2), IMP-8 (n = 12), IMP-16 (n = 1), NDM-1 (n = 5), NDM-2 (n = 1), GIM-1 (n = 4), OXA-23 (n = 69), OXA-72 (n = 2) and OXA-58 (n = 6).

T152

111106-111294

Epistemic_statement

denotes

However, the molecular epidemiology in Germany with a predominance of OXA-48 differs significantly from observations made in other countries like Greece, Israel, USA or the United Kingdom.

T153

111410-111589

Epistemic_statement

denotes

Objectives: The successful worldwide dissemination of carbapenemase producing Enterobacteriaceae is of special concern because of limited therapeutic options and higher mortality.

T154

111590-111900

Epistemic_statement

denotes

While the dissemination of carbapenemase KPC is predominantly bound to distinct Klebsiella pneumoniae strains, spread of OXA-48 and NDM-1 enzymes is mainly due to conjugative transfer of different plasmids carrying these carbapenemase genes and facilitating the transmission among many enterobacterial species.

T155

113489-113687

Epistemic_statement

denotes

Although carbapenemase producing Enterobacteriaceae are still rare in many European countries there is an urgent need of surveillance to prevent further spread of these multidrugresistant pathogens.

T156

113688-113769

Epistemic_statement

denotes

How should we treat double -and triple -resistant Helicobacter pylori in Germany?

T157

113770-113903

Epistemic_statement

denotes

Background and Objective: Enterobacteriaceae have been shown to play a crucial role in the transmission of antimicrobial resistances.

T158

114025-114306

Epistemic_statement

denotes

Dissemination of antibiotic resistance can be due to the transfer of resistant bacteria between different host organisms or by horizontal transfer of resistance properties between isolates of the same or different species and genera within and beyond the family Enterobacteriaceae.

T159

114307-114629

Epistemic_statement

denotes

Especially, resistance to -lactams mediated by production of Extended-spectrum beta-lactamases (ESBL) and resistance to (fluoro)quinolones influenced by different plasmid-mediated quinolone resistance determinants are of concern since they limit dramatically the therapeutic options in both, veterinary and human medicine.

T160

115850-116067

Epistemic_statement

denotes

The RESET network includes different interacting and complementary studies on factors associated with the dissemination of emerging resistance properties in Enterobacteriaceae from humans, animals and the environment.

T161

117049-117231

Epistemic_statement

denotes

Our data show frequent co-resistances to therapeutically relevant antibiotics (ampicillin, aminoglycosides) for enterococci; resistances to antibiotics of last resort are still rare.

T162

117232-117331

Epistemic_statement

denotes

Comparably high rates of vanB VRE suggest a changing epidemiology of van genotypes in recent years.

T163

117695-117791

Epistemic_statement

denotes

Therefore, testing the activity of older and rarely used antibiotics is of high clinical impact.

T164

119012-119194

Epistemic_statement

denotes

Applying a threshold of 16 mm as susceptible in disk diffusion (fosfomycin 200 μg) as recommended by CLSI for E. coli eleven very major errors (10.3%) and no major errors were found.

T165

120326-120513

Epistemic_statement

denotes

Based on the whole genome data the mprF locus, which was previously shown to be associated with daptomycin resistance was re-sequenced in 64 daptomycin resistant and susceptible isolates.

T166

120886-120995

Epistemic_statement

denotes

Sequence analysis of whole genome data revealed a small number of SNPs putatively associated with resistance.

T167

120996-121203

Epistemic_statement

denotes

However, after re-sequencing the corresponding loci in a larger number of resistant and susceptible isolates strong association of resistance to mutations in a certain locus could be confirmed only for mprF.

T168

121301-121502

Epistemic_statement

denotes

Conclusion: Results corroborate the role of mprF-mutations in resistance development towards daptomycin; however further studies must elucidate the complete mechanism leading to reduced susceptibility.

T169

121975-122027

Epistemic_statement

denotes

Data regarding carbapenemases in Germany are scarce.

T170

123180-123364

Epistemic_statement

denotes

Transconjugation experiments were successful only in one strain, however the presence of blaKPC on plasmids could be demonstrated by restriction with S1 endonuclease and Southern Blot.

T171

123656-123763

Epistemic_statement

denotes

The low MIC for carbapenems in some strains emphasizes that detection of carbapenemases can be challenging.

T172

124174-124394

Epistemic_statement

denotes

In this context it is of interest whether czrC and the already known resistance gene cadA (both code for an ATPase based efflux) are disseminated among different clonal lineages of MRSA prevalent in humans and livestock.

T173

124695-124910

Epistemic_statement

denotes

Results: czrC was exclusively associated with MRSA ST398 (20/27 from pigs; 21/23 from humans exposed to pigs; 10/20 infections; 10/10 infections in humans) and contained by a defined SCCmec-element with tandem ccrC.

T174

125349-125536

Epistemic_statement

denotes

Discussion: It can not be excluded that the previous use of zinkoxide ions in conjunction with organic acids as feed additives has selected for czrC and possibility coselected MRSA ST398.

T175

125781-125986

Epistemic_statement

denotes

With respect to multiresistant but methicillin susceptible S. aureus ST30 ("80/80 complex") in the past and use of zinkoxide ointments containing also boronic acid this situation might have been different.

T176

125987-126160

Epistemic_statement

denotes

Introduction: The emergence of healthcare associated infections caused by multidrug-resistant Gram-negative bacteria has become an increasing problem over the past 20 years.

T177

126161-126296

Epistemic_statement

denotes

Colistin, a 'forgotten' antibiotic, has attracted attention, because of its activity against multidrug-resistant Gramnegative bacteria.

T178

126297-126358

Epistemic_statement

denotes

It is, however, not active against Proteeae and Serratia spp.

T179

128351-128453

Epistemic_statement

denotes

Conclusions: Overall, susceptibility to COL seems to be high among Gram-negative pathogens in Germany.

T180

128454-128509

Epistemic_statement

denotes

COL may be considered as an important treatment option.

T181

129717-129801

Epistemic_statement

denotes

MIC to penicillin depended on serogroup: using serogroup B and rare serogroups (e.g.

T182

129983-130075

Epistemic_statement

denotes

Interestingly, 51.9% of serogroup W-135 strains were intermediate susceptible to penicillin.

T183

130192-130341

Epistemic_statement

denotes

Although no resistance was observed for cefotaxime, cefotaxime MICs showed a weak yet significant linear correlation with penicillin MICs (r^2 0.23).

T184

130490-130629

Epistemic_statement

denotes

Due to low rate of nonsusceptibility, no meaningful analyses were possible for antimicrobials rifampicin and ciprofloxacin in meningococci.

T185

130779-130928

Epistemic_statement

denotes

Resistance was significantly more common in non-typeable H. influenzae lacking a polysaccharide capsule (13.0%) compared to capsulate strains (3.7%).

T186

133443-133860

Epistemic_statement

denotes

Discussion: While the EARS-Net-Surveillance limited to invasive isolates from hospitalised patients captures the sector with highest levels of antimicrobial resistance in K. pneumoniae, the extended approach of ARS reveals an emerging problem in outpatient care that physicians should be aware of, even if resistance proportions might be overestimated as samples are more likely to be taken from pre-treated patients.

T187

135252-135291

Epistemic_statement

denotes

451 patients have been examined so far.

T188

135680-135847

Epistemic_statement

denotes

19% of the patients were still H. pylori positive after treatment, which might be explained by the high rate of clarithromycin resistance (29%) within this population.

T189

135848-136040

Epistemic_statement

denotes

In conclusion, these results underline the hypothesis that development of resistance in H. pylori in contrast to other pathogens is dependent on treatment strategies in the individual patient.

T190

136486-136736

Epistemic_statement

denotes

Stratification by federal states shows considerable regional differences (range:1.8-6.4/100,000 inhabitants/year), which were positively correlated to regional MRSA-rates (6.7%-27.3%) generated in ARS (spearman correlation coefficient: 0.74; p=0.04).

T191

136737-136912

Epistemic_statement

denotes

Conclusion: While mandatory reporting of MRSA-bacteraemia serves as an indicator of the situation in hospital care, ARS additionally provides a view on the outpatient setting.

T192

137005-137117

Epistemic_statement

denotes

Nevertheless, the results indicate that in Germany MRSA plays a relevant role in the outpatient setting as well.

T193

137118-137367

Epistemic_statement

denotes

Particularly, high resistance rates in urine samples suggest that further investigations about the epidemiological context in which infections occur and patient characteristics are necessary to assess possible consequences for antibiotic management.

T194

137590-138007

Epistemic_statement

denotes

Wieler 1 , C. Ewers 1 1 Freie Universität Berlin, Institut für Mikrobiologie u. Tierseuchen, Berlin, Deutschland 2 Vet Med Labor GmbH, Ludwigsburg, Halle, Deutschland Introduction: Several studies give evidence for the carriage of Extendedspectrum beta-Lactamases (ESBL) producing E. coli in the feces of wild birds even in remote areas, where the presence of antibiotic selection pressure is assumed to be very rare.

T195

138708-138909

Epistemic_statement

denotes

Genotyping led to the frequent detection of virulence determinants associated with extraintestinal pathogenicity whereas genes associated with intestinal pathogenic pathovars were only rarely observed.

T196

139172-139369

Epistemic_statement

denotes

Among the Mongolian samples we identified several STs, such as ST167 (ancestral group A) or ST648 (hybrid group ABD) which have previously been reported from human clinical ESBL producing isolates.

T197

139596-139732

Epistemic_statement

denotes

Conclusions: Our findings underline the urgent need to unravel the role of wild birds in the spread of antimicrobial resistant bacteria.

T198

139733-139998

Epistemic_statement

denotes

Due to their migration behavior and with respect to the omnipresence of bird´s feces in wild and urban environments, wild birds might represent a non-point source of infection and could by that considerably contribute to the transmission of ESBL producing bacteria.

T199

140564-140738

Epistemic_statement

denotes

The currently used methods require the use of experts to evaluate the result of noise removal, because the methods need some parameters which correlate to the detected noise.

T200

140739-140805

Epistemic_statement

denotes

The adaption/calibration can only be executed by a manual process.

T201

140899-141042

Epistemic_statement

denotes

The focus of this article lies in the development of automated pre-processing method which can reduce the significantly influence of the noise.

T202

141043-141134

Epistemic_statement

denotes

Noise: Generally, in test results, two different types of noise can occur (Wilhelm, 2003) .

T203

141236-141295

Epistemic_statement

denotes

The possible causes of the occurrence are not yet resolved.

T204

141296-141419

Epistemic_statement

denotes

The effects of background noise and signal trend for the repeated execution of sample analysis may lead to varying results.

T205

143535-143678

Epistemic_statement

denotes

Results: Comparing Ulifloxacin vs. Ciprofloxacin and Norfloxacin concordant results could be obtained in 250 of the 267 (93.6%) tested strains.

T206

144320-144464

Epistemic_statement

denotes

For Enterococci following results could be found: Susceptibility to Ciprofloxacin, Norfloxacin and Prulifloxacin was 38%, 42%, 28% respectively.

T207

144559-144694

Epistemic_statement

denotes

Comparing the results of Ciprofloxacin, Norfloxacin and Ulifloxacin concordant results in 250 of 267 strains (93.6%) could be obtained.

T208

144786-144947

Epistemic_statement

denotes

Against gram positive strains Ulifloxacin was slightly less active as Ciprofloxacin and Norfloxacin, but this statement is limited by the low number of isolates.

T209

144948-145172

Epistemic_statement

denotes

Because of some minor differences in the interpretation of the susceptibility pattern testing of Ulifloxacin and/or other chinolones resistance testing seems to be noteworthy if therapy with this fluorochinolone in intended.

T210

145173-145503

Epistemic_statement

denotes

Impact of thymidine on the antimicrobial activities of trimethoprim/sulfamethoxazole, 5-iodo-2'-deoxyuridine, and rifampicin against Staphylococcus aureus Objectives: A treatment option against S. aureus in general and MRSA in particular is trimethoprim/sulfamethoxazole (SXT) either alone or in combination with rifampicin (RIF).

T211

145667-145878

Epistemic_statement

denotes

However, the antimicrobial activity of SXT can be antagonised by bacterial utilisation of thymidine, which can be present in infected and/or inflamed tissues such as the airways of cystic fibrosis (CF) patients.

T212

145879-146132

Epistemic_statement

denotes

The aim of this study was to determine thymidine concentrations in the sputa of CF patients and to analyse the antimicrobial activity of SXT, 5-iodo-2´-deoxyuridine (IdUrd) and RIF alone and in combination against S. aureus in the presence of thymidine.

T213

146906-147073

Epistemic_statement

denotes

Conclusions: Our data suggest that SXT in combination with rifampicin may fail to cure clinical S. aureus infections in tissues with elevated thymidine concentrations.

T214

147074-147220

Epistemic_statement

denotes

SXT in combination with a thymidine kinase inhibitor, however, may become an interesting antimicrobial combination for this setting in the future.

T215

147282-147582

Epistemic_statement

denotes

Non-nucleoside analogs as bacterial thymidine kinase inhibitors identified by multi-step virtual screening Objectives: The antimicrobial activity of folic acid antagonists can be antagonized by thymidine as detected in tissues with necrotic cells such as pus and sputum from cystic fibrosis patients.

T216

147792-148025

Epistemic_statement

denotes

However, several bacterial species including S. aureus possess an alternative pathway for synthesis of intracellular dTMP by uptake of extracellular thymidine and subsequent intracellular phosphorylation to dTMP via thymidine kinase.

T217

148844-149023

Epistemic_statement

denotes

Conclusions: Our study demonstrates that multi-step virtual screening can help identify bioactive substances from a large screening compound pool with limited experimental effort.

T218

149024-149182

Epistemic_statement

denotes

Rapid focusing on promising candidate structures was possible, so that inhibitors of bacterial thymidine kinase with non-nucleoside scaffolds were identified.

T219

149615-149915

Epistemic_statement

denotes

Schmidt 1 1 ZMBE, Infektiologie, Münster, Deutschland 2 UKM, Institute of Experimental Musculoskeletal Medicine, Münster, Deutschland Cell-permeable proteins such as 'cell-penetrating peptides (CPP)' have the ability to cross cellular membranes, either alone or in association with a bioactive cargo.

T220

150244-150379

Epistemic_statement

denotes

This might contribute to systemic effects on innate immunity and, furthermore, suggests potential therapeutic applications of YopM e.g.

T221

150414-150719

Epistemic_statement

denotes

Hence, we were interested to investigate whether YopM might have the potential to act as an immune modulating molecule by exhibiting beneficial effects on inflammation and the production of cytokines that maintain the inflammatory processes linked to autoimmune diseases such as rheumatoid arthritis (RA).

T222

151256-151354

Epistemic_statement

denotes

With respect to a potential in vivo application of YopM, we injected YopM intra-articularly (i.a.)

T223

152114-152358

Epistemic_statement

denotes

These encouraging results combined with the possibility for focused topical applications in skeletal joints underline and strengthen the potential of YopM as a novel pathogen-derived immune modulatory agent for the treatment of inflammatory RA.

T224

152359-152693

Epistemic_statement

denotes

Comparison of genotypic, proteotypic and phenotypic methods for the identification of bacteria M. Patel 1 , U. Herber* 1 1 Accugenix, Marketing, Newark, Deutschland Accurate classification of unknown bacterial isolates is an essential first step in understanding the impact these organisms have on an environmental monitoring program.

T225

152694-152914

Epistemic_statement

denotes

There are many methods, technologies, and strategies utilized to determine the identity of unknown microorganisms, however, the selection of these methods is often impacted by more than the performance of the technology.

T226

153331-153471

Epistemic_statement

denotes

When identifications are based on phenotypic characteristics, the methods are more subjective and results can be impacted by many variables.

T227

154115-154219

Epistemic_statement

denotes

These microbial identification methods were used to analyze 60 unknown environmental bacterial isolates.

T228

154946-155014

Epistemic_statement

denotes

The pathogenesis of psoriasis is complex and not clearly understood.

T229

155015-155129

Epistemic_statement

denotes

Ongoing research indicates that immune T-cells appear to play a dominant role for the development of this disease.

T230

155919-156017

Epistemic_statement

denotes

Therefore, YopM might be applicable as a topical therapeutic agent for the treatment of psoriasis.

T231

156018-156183

Epistemic_statement

denotes

To investigate whether YopM might be functional as an immune-modulator for the treatment of psoriasis, we utilized the murine imiquimod (IMQ)induced psoriasis model.

T232

156344-156449

Epistemic_statement

denotes

Therefore, this model could serve for the analysis of pathogenic mechanisms in psoriasis-like dermatitis.

T233

157522-157662

Epistemic_statement

denotes

The genomic island is integrated within the tRNA Pro gene (lpc2778) and can exist in an integrated chromosomal or an episomal circular form.

T234

157852-157976

Epistemic_statement

denotes

By deleting the int-1 gene, we could demonstrate that the excision and forming of an episomal circle is integrase dependent.

T235

157977-158149

Epistemic_statement

denotes

First experiments with a mutant lacking the vir region, also indicate a growth dependent regulation of the alteration between the integrated and the circular form of Trb-1.

T236

158150-158294

Epistemic_statement

denotes

The whole genomic island can be transferred to other Legionella strains and integrated site-specifically into the genome of the transconjugants.

T237

158979-159114

Epistemic_statement

denotes

We could demonstrate that both genomic islands can exist in an integrated chromosomal and an exercised episomal form, similar to Trb-1.

T238

159862-160065

Epistemic_statement

denotes

Although a substantial amount of information about the GSLreceptors for Shiga toxins (Stxs), the major virulence factors of EHEC, is available, less is known about the receptors for EHEC bacterial cells.

T239

160730-160929

Epistemic_statement

denotes

In the present study the potential of GSL recognition by various EHEC O157 strains was investigated employing neutral GSLs and sialylated GSLs (=gangliosides) from different types of mammalian cells.

T240

161549-161773

Epistemic_statement

denotes

In conclusion, this study may help to better understand host-pathogen interactions and in particular the adhesion process of EHEC toward target cells and, moreover, to develop strategies to prevent and treat EHEC infections.

T241

162800-163002

Epistemic_statement

denotes

Microdomain association of GSLs is believed to be the linchpin in effective binding, internalization and subcellular routing of GSL-binding AB5-toxins such as Shiga toxin (Stx) to intracellular targets.

T242

163796-163944

Epistemic_statement

denotes

Studies on the subcellular distribution of Stx receptors in both cell types showed their predominant association with and enrichment in lipid rafts.

T243

167345-167467

Epistemic_statement

denotes

These promising initial data suggest further characterization of the compounds and an evaluation of putative applications.

T244

167818-168112

Epistemic_statement

denotes

EF-Tu from Escherichia coli has been shown to polymerize in vitro and a recent study provided evidence that the protein serves besides its function in translation another vital role in Bacillus subtilis: it affects cell morphology, apparently via interaction with the cytoskeleton protein MreB.

T245

168113-168236

Epistemic_statement

denotes

In rod-shaped bacteria the actin-ortholog MreB is thought to direct incorporation of cell wall material into the side wall.

T246

168237-168395

Epistemic_statement

denotes

Surprisingly, chlamydiae harbor, despite their spherical shape and the absence of a cell wall, MreB and we recently proved in vitro activity for this protein.

T247

168607-168732

Epistemic_statement

denotes

Additionally, co-polymerization assays revealed interactions between the elongation factor and the cytoskeletal protein MreB.

T248

169235-169337

Epistemic_statement

denotes

This ubiquitous bacterium can cause two forms of legionellosis -Legionellapneumonia and Pontiac fiver.

T249

169446-169649

Epistemic_statement

denotes

Although the failure in the therapy occurs from time to time, there are no reports about the isolation of the macrolide or quinolon-resistant Legionella mutants from the patients and environment to date.

T250

170615-170775

Epistemic_statement

denotes

The reduced ecological fitness of the macrolide resistant mutants might be an explanation for the lack occurrence of resistant strains under natural conditions.

T251

170776-170955

Epistemic_statement

denotes

For more than a hundred years, it has been known that patients with solid tumors who concomitantly suffer from a bacterial infection experience a regression of their tumor burden.

T252

170956-171048

Epistemic_statement

denotes

Still, the phenomenon of bacterial tumor targeting and lysis remains only poorly understood.

T253

171234-171360

Epistemic_statement

denotes

Amid several theoretically interesting approaches, we focused our efforts on immunosuppressive and pro-inflammatory cytokines.

T254

171361-171547

Epistemic_statement

denotes

The immunosuppressive cytokines are supposed to expand the inoculum in the tumor and should enable the bacteria to penetrate the host immune defense shielding the tumor from total lysis.

T255

171548-171712

Epistemic_statement

denotes

On the other hand, the proinflammatory cytokines should attract inflammatory cells, boost NK cell and CD8+ T-cell activity and eventually lead to tumor vaccination.

T256

171713-171845

Epistemic_statement

denotes

Here, we are going to present first results with recombinant Interleukin-10 and Interleukin-12 fusion proteins expressed in E. coli.

T257

173422-173545

Epistemic_statement

denotes

However, while EDTA has found widespread application as a conservative, its clinical use is hampered by toxic side effects.

T258

174995-175200

Epistemic_statement

denotes

As this antibiotic has been in clinical use over the last 50 years without serious side effects having been reported, it constitutes a promising candidate for the development of new therapeutic strategies.

T259

175503-175610

Epistemic_statement

denotes

Their mutual agreement and factors influencing the results have not been studied in detail in South Africa.

T260

175611-175734

Epistemic_statement

denotes

Thus a study was conducted at 15 sampling sites in the Eastern Cape Province of South Africa to address this knowledge gap.

T261

177164-177302

Epistemic_statement

denotes

If a suspension of the sediment matter on-site took place, this would lead to a change in the bacterial concentrations between 0 and 24 %.

T262

177507-177618

Epistemic_statement

denotes

Conclusions: Re-suspension of sediment particles can compromise the results of microbial water quality testing.

T263

177619-177797

Epistemic_statement

denotes

Temperature fluctuations between 10 and 32 ºC are not expected to influence the applicability of the hydrogen-sulphide test in detection of faecal contamination of surface water.

T264

178536-178766

Epistemic_statement

denotes

A sustainable in-time management of emulsion paint production should rely on fast quantitative MC analysis of products and their effective separation, thereby minimizing preservative input and waste of contaminated emulsion paint.

T265

180392-180548

Epistemic_statement

denotes

Conclusions: Further development effort would be needed to optimize sample preparation with special focus on removal of inhibitory emulsion paint compounds.

T266

180549-180715

Epistemic_statement

denotes

All methods should run on (or must easily be adaptable to) integrated sample and analysis robotics applying qRT-PCR, automated analysis and interpretation of results.

T267

180716-180922

Epistemic_statement

denotes

This requirement is crucial since a final qRT-PCR based QC strategy should be able to manage the emulsion paint production without interaction of human PCR experts in a model environment at JWO in Coesfeld.

T268

181308-181454

Epistemic_statement

denotes

By performing studies on the interactions present in multispecies biofilms, basic knowledge on several aspects of sociomicrobiology can be gained.

T269

181455-181577

Epistemic_statement

denotes

The aim of this work was to assess the role of interspecies interactions in species biofilm formation and characteristics.

T270

182722-182875

Epistemic_statement

denotes

A range of interactions has been observed among microorganisms in biofilms, including competitive, mutualistic, antagonistic and commensal relationships.

T271

184188-184334

Epistemic_statement

denotes

These proteins are presumably highly antigenic due to the exposure to the host's immune system and may be used as antigens in diagnostic purposes.

T272

184335-184556

Epistemic_statement

denotes

In this study could be demonstrated that recombinantely produced Cj0069, one of the secreted proteins, has a similar sensitivity and specificity compared to the already and commercially established antigens OMP18 and P39.

T273

185982-186193

Epistemic_statement

denotes

Conclusion: This study reveals that hreP and the pyp genes are part of a complex regulatory network that is repressed by H-NS, further underlining our hypothesis that these genes have been acquired horizontally.

T274

187135-187333

Epistemic_statement

denotes

Depending on the serovar, host species, age and immune status the course of disease can range from asymptomatic carriage or localized acute diarrhea to severe systemic infections with fatal outcome.

T275

187334-187673

Epistemic_statement

denotes

To evaluate possible host differences in flagellin recognition in human and animal cells and subsequent induction of immunostimulatory signalling cascades, we have used the activation of transcription factor nuclear factor -B (NF-B) in NF-B reporter cell lines of different species origins that express a luciferase during NF-B activation.

T276

188188-188370

Epistemic_statement

denotes

The varying behaviour and sensing of Salmonella flagellin in different host species might contribute to the different outcome of infection and host adaptation of Salmonella serovars.

T277

188371-188537

Epistemic_statement

denotes

Shiga toxins (Stxs) are secreted by Stx-producing Escherichia coli (STEC) that cause diarrhea, bloody diarrhea and potentially lethal hemolytic-uremic syndrome (HUS).

T278

188930-189211

Epistemic_statement

denotes

Although preferential Stxmediated damage of glomerular microvascular endothelial cells (GMVECs) is known as the major mechanism underlying HUS caused by STEC, the exact nature of the Stx receptor GSLs of GMVECs including the expression of different lipoforms remains to be defined.

T279

190323-190424

Epistemic_statement

denotes

This higher sensitivity of GMVECs correlated with the enhanced expression of Stx-receptors in GMVECs.

T280

190425-190863

Epistemic_statement

denotes

However, as GSLs are believed to localize abundantly in lipid rafts tightly associated with cholesterol and raftassociated membrane proteins and since lipid raft association of Stx receptors is assumed as a functional prerequisite for Stx-mediated cytotoxicity, future investigations on the subcellular distribution of GSLs in GMVECs are required to explore the functional role of the molecular assembly of GSLs in microdomains of GMVECs.

T281

191196-191355

Epistemic_statement

denotes

Together with the CagA effector protein, it is encoded on the cag pathogenicity island (cag-PAI), the presence of which is associated with more severe disease.

T282

191819-191915

Epistemic_statement

denotes

Therefore, it is likely that H. pylori is able to modulate the immune response to its advantage.

T283

192001-192149

Epistemic_statement

denotes

It has been shown before that macrophages aggregate under the influence of the Cag T4SS, and that CagA can be translocated into these cells as well.

T284

192624-192774

Epistemic_statement

denotes

The migration assays suggest that H. pylori infection results in a chemotactic defect of phagocytic cells and in an inhibition of phagocyte migration.

T285

192775-192912

Epistemic_statement

denotes

Infection with H. pylori mutants showed that the inhibitory effect on human granulocyte migration is likely to be caused by the Cag T4SS.

T286

192913-193065

Epistemic_statement

denotes

In conclusion, our results suggest that interaction of the Cag T4SS with phagocytic cells may contribute to immune evasion and persistence of H. pylori.

T287

193185-193387

Epistemic_statement

denotes

New 027 outbreak strains with global spreading are characterised by toxin A, B and binary toxin expression, mutations of a potential toxin repressor gene (tcdC), and increased toxin production in vitro.

T288

194433-194608

Epistemic_statement

denotes

Interestingly, the rate of various C. difficile genotypes was different between children and adults with high percentage of non-toxigenic strains in the pediatric group (50%).

T289

194609-194844

Epistemic_statement

denotes

Using an institutional database the genetic relationship between the various slpAST was analysed showing clustering in at least three major genetic groups subdivided in different subgroups with close association to known PCR ribotypes.

T290

194929-195016

Epistemic_statement

denotes

We could show that 027 rates recently decrease in our previously high-prevalent region.

T291

195017-195138

Epistemic_statement

denotes

We hypothesize that the rates of epidemic strains and presumably also strain specific virulence may change over time e.g.

T292

195139-195201

Epistemic_statement

denotes

due to host adaptation and possibly also in different regions.

T293

195202-195277

Epistemic_statement

denotes

Emergence of new epidemic C. difficile strains may occur at any time again.

T294

195429-195569

Epistemic_statement

denotes

SlpAST is a well standardized method to identify current epidemic C. difficile strains but also strains of still unknown epidemic relevance.

T295

195853-196012

Epistemic_statement

denotes

This protein translocation results in altered host cell gene expression profiles and cytoskeletal rearrangements, and it has been linked to cancer development.

T296

196191-196381

Epistemic_statement

denotes

Recently, it has been shown that the Cag type IV secretion apparatus binds to integrin molecules as receptors on host cells, and that several Cag components are involved in this interaction.

T297

196479-196722

Epistemic_statement

denotes

Previous studies have identified the cagI gene as an essential gene for translocation of CagA into host cells, but there have been conflicting results as to its requirement for stimulation of interleukin-8 (IL-8) secretion by epithelial cells.

T298

196723-196976

Epistemic_statement

denotes

Since the cagI gene overlaps and is co-transcribed with the cagL gene encoding another integrin-interacting protein essential for Cag functionality, this discrepancy might be due to transcriptional effects of the resistance markers used for mutagenesis.

T299

197132-197324

Epistemic_statement

denotes

The absence of several components of the secretion apparatus has an impact on CagI and CagL protein levels, indicating that (partial) assembly of the apparatus is required for their stability.

T300

197524-197651

Epistemic_statement

denotes

Taken together, our results are consistent with the assumption that CagI and CagL form a complex at the bacterial cell surface.

T301

198251-198416

Epistemic_statement

denotes

This was thought to be associated with the emergence of a more virulent strain, Clostridium difficile PCR ribotype 027, which was first reported in Germany in 20007.

T302

199903-200033

Epistemic_statement

denotes

Hospital discharge diagnosis data for 2010 are not yet available (2009: 120.8 CDI diagnoses/100.000 discharged hospital patients).

T303

200328-200430

Epistemic_statement

denotes

Discussion: The continuing increase of CDI cases that peaked in 2010 shows the urgent need for action.

T304

200431-200481

Epistemic_statement

denotes

The nature of this increase is not yet understood.

T305

200482-200540

Epistemic_statement

denotes

An improved characterization of cases is therefore needed.

T306

200742-200786

Epistemic_statement

denotes

This will help to focus preventive measures.

T307

201902-202016

Epistemic_statement

denotes

Preliminary analysis of the data showed that the isolates can be grouped into approximately 50 distinct ribotypes.

T308

202166-202284

Epistemic_statement

denotes

Discussion: Analysis of a large number of c. difficile from an expansive urban area has not been described in Germany.

T309

202285-202620

Epistemic_statement

denotes

It is interesting to scrutinise such data as one may be able to determine if the increasing incidence of CDAD is perhaps, unlike the case in North Anmerica, not associated with a specific clonal spread and therby also determine if the change is perhaps due to changes in medical practice rather than a shift in the bacterial virulence.

T310

202621-202952

Epistemic_statement

denotes

Our results show that the vast majority of the isolates possesed both toxin A and B genes and that only few [12.6 the binary toxin gene, a disproportionate number of these [60.6 %] however were located in isolates positive for tcdA and negative for tcdB genes, which only accounted for 7.8 % of the total number of isolates tested.

T311

203499-203573

Epistemic_statement

denotes

Thus, giardiasis is a major public and veterinary health concern globally.

T312

203574-203673

Epistemic_statement

denotes

It remains unclear to what degree it is a zoonosis and what determines its pathogenicity to humans.

T313

203674-203865

Epistemic_statement

denotes

To assess these issues a Gd biobank shall be generated to link epidemiological data with functional characteristics of clinical isolates and as a means to identify virulence associated genes.

T314

203866-204029

Epistemic_statement

denotes

We hypothesize that potential virulence markers are enzymes released by Giardia upon colonization of the small instestine and interaction with the host epithelium.

T315

204030-204285

Epistemic_statement

denotes

Especially the Gd arginine deiminase (ADI) that converts arginine to citrulline and ammonia shall be investigated as possible virulence and pathogenicity factor of Gd, because arginine plays a critical role in antimicrobial mechanisms and immune response.

T316

204286-204508

Epistemic_statement

denotes

The sequencevariation of ADI will be determined by cloning adi from Gd isolates being collected in the biobank and sequence variants will be functionally characterized by expressing the respective recombinant ADI proteins.

T317

204509-204652

Epistemic_statement

denotes

Finally, correlation between enzyme function and clinical pathology shall be investigated on basis of Gd isolates related epidemiological data.

T318

204653-204704

Epistemic_statement

denotes

We will present the establishment of this workflow.

T319

206911-207081

Epistemic_statement

denotes

Using a murine infection model we discovered distinct correlations between the metabolism of the tested amino acids and the persistence of C. jejuni in different tissues.

T320

207219-207362

Epistemic_statement

denotes

Gaussia princeps luciferase (Gluc) can be used to monitor type I protein secretion in Salmonella enterica serovar Typhimurium T. Wille 1 , R.G.

T321

207606-207671

Epistemic_statement

denotes

Data about the applicability of Gluc in bacteria is very limited.

T322

207672-207817

Epistemic_statement

denotes

Given the small size, high activity and co-factor independence of Gluc, it might be especially suited to monitor secretion of bacterial proteins.

T323

208581-208741

Epistemic_statement

denotes

We could show that a C-terminal moiety of SiiE including immunoglobulin (Ig) domain 53 is essential and sufficient mediating type I-dependent secretion of Gluc.

T324

208847-208929

Epistemic_statement

denotes

Discussion: In conclusion, Gluc can be used to monitor protein secretion via T1SS.

T325

209243-209417

Epistemic_statement

denotes

Helicobacter pylori BCS 100 genome variability and potential virulence determinants during an experimental human infection L. Kennemann* 1 , T. Aebischer 2 , S. Kuhn 1 , T.F.

T326

209819-209932

Epistemic_statement

denotes

Much less is known about genomic adaptations that may occur in the first months of infection of a new human host.

T327

209933-210210

Epistemic_statement

denotes

Here, we present the complete genome sequence of H. pylori strain BCS 100 (H1), a cagPAI deficient isolate that has been used for several human challenge studies in the US and Germany, and draft sequences of reisolates obtained from four volunteers after 3 months of infection.

T328

210211-210361

Epistemic_statement

denotes

Results: The genome sequence of H. pylori challenge strain H1 was obtained by 454 sequencing and subsequent gap closure by targeted Sanger sequencing.

T329

210984-211200

Epistemic_statement

denotes

Unexpectedly, a previously unknown variant of the input strain was detected in several volunteers which differed from the 454 sequenced input clone H1 by 86 SNPs and three clusters of nucleotide polymorphisms (CNPs).

T330

211201-211368

Epistemic_statement

denotes

This variant was commonly detected among the additional reisolates from the study, suggesting strong in vivo selection favoring this subpopulation in some human hosts.

T331

212616-212808

Epistemic_statement

denotes

We attempt to localize the distinct binding regions of these proteins within the receptor and we want to determine, whether binding of CagA to ITGB1 is an essential step in CagA translocation.

T332

212999-213196

Epistemic_statement

denotes

These data can help to propose a new model of interaction between the pathogenic H. pylori and the eukaryotic cell, mediated by specific interactions of the cag-T4SS and the ITGB1 of the host cell.

T333

213615-213747

Epistemic_statement

denotes

ACI outbreak specific findings included an association to university hospitals, to intensive care units, and to surgery departments.

T334

213748-213902

Epistemic_statement

denotes

PAE outbreaks were associated with significantly less use of isolation precautions, less frequently closure of wards, and less use of protective clothing.

T335

214572-214694

Epistemic_statement

denotes

However, from our point of view currently there is no MRGN bacterium that should be totally disregarded with this respect.

T336

214695-214891

Epistemic_statement

denotes

Essen, Deutschland 3 University Hospital Essen, Hospital Hygiene, Essen, Deutschland Introduction: Postoperative wound infections generally cause considerable extra morbidity, mortality and costs.

T337

216511-216642

Epistemic_statement

denotes

Attention should be paid to antibiotic prophylaxis and Methicillin-resistant Staphylococcus aureus (MRSA) nasal carriage treatment.

T338

216643-216733

Epistemic_statement

denotes

In this study BMI >30 and high blood-glucose levels were associated with wound infections.

T339

216734-216803

Epistemic_statement

denotes

Overall the rate of SSIs was low, but further surveillance is needed.

T340

217015-217176

Epistemic_statement

denotes

Mikrobiologie u.Krankenhaushygiene, Hannover, Deutschland Background: Hand hygiene is the most effective measure for preventing infections related to healthcare.

T341

217177-217510

Epistemic_statement

denotes

This study aims to evaluate the hand hygiene compliance in a German university hospital overall and in addiction to the professional status after implementation of the national hand hygiene campaign "Aktion Saubere Hände in 2008.This is the largest nationwide survey on intensive care units (ICU) in a university hospital in Germany.

T342

218412-218511

Epistemic_statement

denotes

No significant correlation between hand rub consumption and hand hygiene compliance was calculated.

T343

219579-219824

Epistemic_statement

denotes

Effective and rapid analysis of nosocomial outbreaks using the DiversiLab semi-automated repetitive sequence-based PCR test system Objectives: Rapid and sensitive methods are essential for typing and monitoring of hospital associated infections.

T344

219963-220252

Epistemic_statement

denotes

Aim of the study was to evaluate the usefulness and accuracy of the DiversiLab system for bacterial strain typing and determination of genetic relatedness of strains associated with nosocomial outbreaks and integration of the system in the workflow of a routine microbiological laboratory.

T345

220830-221017

Epistemic_statement

denotes

The same result could be observed in the 26 multi-resistant A. baumannii strains, where strains showed identical cluster formation (into 3 separate clusters) and very similar dendrograms.

T346

221967-222130

Epistemic_statement

denotes

-Results on the DiversiLab system could be obtained in a short period (8-24h), which is an essential advantage in rapid analysis of hospital associated infections.

T347

222380-222496

Epistemic_statement

denotes

However, often their actual ability of killing germs and their overall practicability in daily life remains unknown.

T348

222722-222861

Epistemic_statement

denotes

According to the manufacturer's instructions the wand should be used as close as possible and no more than one-half inch above the surface.

T349

222862-222978

Epistemic_statement

denotes

As stated in the operating manual, a 90% elimination of S. aureus would be expected within 12 sec by this procedure.

T350

223969-224196

Epistemic_statement

denotes

However, when using such a device for disinfection purpose in daily life, one has to keep in mind that 20 sec UV-C light exposition time was necessary in order to properly disinfect a rather small surface area from enterococci.

T351

224290-224453

Epistemic_statement

denotes

So there might be few opportunities when such a device could be a useful tool, but it seems less helpful on larger exterior due to time necessary for disinfection.

T352

225028-225168

Epistemic_statement

denotes

Different factors can control the survival of enteric viruses in aquatic environments such as temperature, sunlight, pH, and organic matter.

T353

225169-225277

Epistemic_statement

denotes

However, little is known about the effect of the flow rate on the concentration of viruses in surface water.

T354

226391-226475

Epistemic_statement

denotes

Moreover, no correlation between microbiological parameters and flow rate was found.

T355

226476-226590

Epistemic_statement

denotes

Further investigations are needed to characterize hydrological factors influencing enteric viruses in river water.

T356

226812-227217

Epistemic_statement

denotes

Homogeneous distribution of phenotypic characteristics in clonally unrelated Pseudomonas aeruginosa isolates from technical water systems H. Petry-Hansen* 1 , J. Hanke 1 , J. Heise 1 , H.-C. Flemming 1 , J. Wingender Biofilm Centre, Abteilung Aquatische Mikrobiologie, Essen, Deutschland P. aeruginosa is an opportunistic pathogen ubiquitously found in water environments where it can persist in biofilms.

T357

227218-227372

Epistemic_statement

denotes

Cells released from biofilms contaminate the water phase and pose a potential threat to human health, especially when occurring in man-made water systems.

T358

227373-227469

Epistemic_statement

denotes

The genotypic and phenotypic variability of P. aeruginosa in technical water systems is unknown.

T359

227871-228255

Epistemic_statement

denotes

For 77 representative strains and all seven reference strains the following characteristics were analyzed in order to reveal possible correlations between water source and genotypic as well as phenotypic characteristics: colony morphology, pigment production, hemolysis, cell surface hydrophobicity, biofilm formation, resistance against antibiotics and occurrence of virulence genes.

T360

229336-229470

Epistemic_statement

denotes

No correlation between phenotypic and genotypic traits, and between these characteristics and the origin of the strains were detected.

T361

229671-229791

Epistemic_statement

denotes

There seem to be no selection of a specific genotypic or phenotypic variant of P. aeruginosa in technical water systems.

T362

230116-230195

Epistemic_statement

denotes

Knowledge about the real frequency of nosocomial infections in Germany is rare.

T363

230854-230921

Epistemic_statement

denotes

Results: Overall, 1,047 in-patients could be included in the study.

T364

232380-232550

Epistemic_statement

denotes

Thorax-, Transplantationsund Gefäßchirurgie, Hannover, Deutschland Background: Hand hygiene is the most effective measure for preventing infections related to healthcare.

T365

232551-232700

Epistemic_statement

denotes

This study aims to evaluate the hand hygiene behaviour of health care workers in a German university hospital in treatment of special patient groups.

T366

232886-233043

Epistemic_statement

denotes

They are high risk patients for developing healthcare associated infections due to the high number of devices, the long hospital stays and immunosuppression.

T367

234647-234792

Epistemic_statement

denotes

Once the number of infected persons including hospital staff climbs to a threshold hospital departments may be closed or even the whole hospital.

T368

234793-235004

Epistemic_statement

denotes

Medical and administrative staff members especially those responsible for hospital hygiene management and infection control have a need to know where infectious patients are situated or should be transferred to.

T369

235178-235320

Epistemic_statement

denotes

In case of an outbreak admission, discharge and transfer (ADT) operations can be monitored, controlled and analysed retrospectively over time.

T370

235532-235660

Epistemic_statement

denotes

The text code allows for displaying multiple infections and is likely to become the preferred standard of the hospital operator.

T371

235661-235762

Epistemic_statement

denotes

So far Norovirus, ESBL, MRSA, Clostriods and other infections can be differentiated in the dashboard.

T372

236758-237009

Epistemic_statement

denotes

PROHIBIT aims to analyse existing guidelines and practices to prevent healthcare associated infections (HAI) in Europe, to identify factors that influence compliance with best practices and to test the effectiveness of interventions of known efficacy.

T373

237997-238104

Epistemic_statement

denotes

Seven of the 16 guidelines rate the scientific level of supporting evidence and strength of recommendation.

T374

238105-238212

Epistemic_statement

denotes

All but one guideline explicitly recommend placing symptomatic patients in a single room whenever possible.

T375

238213-238302

Epistemic_statement

denotes

Cleaning or disinfection of frequently touched surfaces is recommended in all guidelines.

T376

238303-238463

Epistemic_statement

denotes

However, only 13 include specific recommendation about disinfectants; out of these 11 prefer chlorine based solutions as specified in the ECDC guidance of 2008.

T377

238464-238515

Epistemic_statement

denotes

There is variation in hand hygiene recommendations.

T378

238876-239007

Epistemic_statement

denotes

In the UK and Ireland public reporting of CDI rates of individual hospitals has been established since 2007 and 2008, respectively.

T379

239176-239264

Epistemic_statement

denotes

Furthermore, there is important variation in scope and detailing of the recommendations.

T380

239265-239355

Epistemic_statement

denotes

The majority of guidelines do not rate the scientific level or strength of recommendation.

T381

239687-239797

Epistemic_statement

denotes

However, some technical challenges have to be taken into consideration to assure a safe use of these products.

T382

239798-239880

Epistemic_statement

denotes

Recently, it has been shown, that active ingredients of surface disinfectants e.g.

T383

239881-240010

Epistemic_statement

denotes

quaternary ammonium compounds can adsorp to the fabrics of wipes and impair the efficacy of the disinfectants significantly (1) .

T384

240110-240206

Epistemic_statement

denotes

Therefore, it was our aim to develop an easy and reproducible test method for this product type.

T385

240315-240466

Epistemic_statement

denotes

OR-tiles according to DGHM (2) were used as test surfaces and a standardized technique for direct application of the soaked wipes has been established.

T386

240467-240679

Epistemic_statement

denotes

In addition, the amount of disinfectant applied to the surface has been investigated Results: Our results show that the suggested assay is suitable to test the practice like efficacy of disinfectant wipe systems.

T387

240848-241027

Epistemic_statement

denotes

There is a strong correlation between the amount of impregnation solution and the amount that can be transferred on the surface which is mandatory for the efficacy of the product.

T388

241028-241251

Epistemic_statement

denotes

We were able to show that the amount of disinfectant that can be transferred from a wipe onto a surface is significant lower than the amounts that are applied on the test carriers in the current published standards (2, 3) .

T389

241252-241389

Epistemic_statement

denotes

Discussion: Now, a reproducible and easy standard method is available that can be used to show the microbicidal efficacy of wipe systems.

T390

241390-241572

Epistemic_statement

denotes

The authors strongly recommend testing the microbicidal efficacy of the wipe systems before practical use and before introducing these systems in positive lists such as VAH and SFHH.

T391

241932-242178

Epistemic_statement

denotes

In May 2011, a large outbreak of an O104:H4 STEC strain (HUSEC 41) expressing an ESBL-positive phenotype occurred with a hot spot in Schleswig-Holstein leading to great challenges in the laboratory diagnosis and infection control in the hospital.

T392

243086-243178

Epistemic_statement

denotes

For all patients displaying symptoms of HUS, STEC ESBL infection could be confirmed (18/18).

T393

243269-243327

Epistemic_statement

denotes

No causative pathogen could be identified in 16 specimens.

T394

243791-243879

Epistemic_statement

denotes

Medical face masks were suggested only for procedures with potential aerosol production.

T395

244595-244789

Epistemic_statement

denotes

To avoid misdiagnosis potentially guiding false initial therapy or infection control measures rapid screening diagnostic methods are required and have been developed by specialized laboratories.

T396

244790-244993

Epistemic_statement

denotes

However, taking into account the inflation-like increasing number of newly suspected cases, the majority of laboratories has become overloaded, and the risk of delayed diagnosis increases proportionally.

T397

245219-245408

Epistemic_statement

denotes

Pathogens to be detected include Shiga-like Toxin producing E.coli, thus we assumed that also the novel variant which is Shigatoxin 1 negative but Shigatoxin 2 positive could be identified.

T398

246026-246141

Epistemic_statement

denotes

Patients can be monitored more closely by the clinicians and test results associated to the clinical course of HUS.

T399

246382-246458

Epistemic_statement

denotes

or Clostridium difficile can be administered the correct antibiotic therapy.

T400

246459-246767

Epistemic_statement

denotes

The Luminex technology is widely available and the assays procedure is rather simple with a total hands-on time of less than 5 hours and a sample capacity of up to 96 samples per run, the assays is suitable for high throughput analyses and thus will cover the peaks in the epidemiological outbreak situation.

T401

249068-249188

Epistemic_statement

denotes

The phenotype with all antimicrobials tested sensitive may indicate a community rather than a nosocomial primary source.

T402

249189-249334

Epistemic_statement

denotes

We assume that after introduction of the strain -maybe by the family of the twins first affected -further nosocomial transmissions have occurred.

T403

249335-249372

Epistemic_statement

denotes

However, the parents were not tested.

T404

249707-249866

Epistemic_statement

denotes

Objective: To perform a prospective in-hospital surveillance of salmonella infection in order to detect possible nosocomial cases in an acute hospital setting.

T405

249867-250063

Epistemic_statement

denotes

Methods: In three tertiary care hospitals all patients with detection of salmonella species were investigated in respect to whether the detection occurred later than 48 h after hospital admission.

T406

251164-251259

Epistemic_statement

denotes

Conclusion: A systematic surveillance of all salmonella-cases identified rare nosocomial cases.

T407

251260-251374

Epistemic_statement

denotes

Food available at food providers near the hospital should be considered if nosocomial salmonella infection occurs.

T408

251618-251732

Epistemic_statement

denotes

Objective: Human Adenovirus (HAdV) can cause severe infections especially in haemato-oncologic pediatric patients.

T409

251733-251836

Epistemic_statement

denotes

In our hospital contactand droplet-precautions are recommended when infections with HAdV are suspected.

T410

251837-252026

Epistemic_statement

denotes

Despite this recommendation HAdV was identified in stool and nasopharyngeal secretion samples of five children in a pediatric haematooncology ward within a two week period in February 2010.

T411

252093-252238

Epistemic_statement

denotes

As a high compliance with precautions in ward staff was observed, the theory of an outbreak with patient to patient transmissions was questioned.

T412

253412-253551

Epistemic_statement

denotes

Possible reasons for the observed cluster may be transmission from parents or siblings or the reactivation of HAdV under immunosuppression.

T413

253552-253678

Epistemic_statement

denotes

Improved education and information of parents and other family members might be a useful additional effort in pediatric wards.

T414

253679-253818

Epistemic_statement

denotes

Objectives: The role of infected and/or colonized health care workers (HCWs) as a potential source of a nosocomial outbreak is yet unclear.

T415

253819-253971

Epistemic_statement

denotes

The present study summarizes data from such outbreaks in order to elucidate areas of special interest and to clarify potential reasons for transmission.

T416

255788-255913

Epistemic_statement

denotes

Conclusion: Nosocomial outbreaks caused by staff are an important problem in the field of epidemiology and infection control.

T417

255914-256038

Epistemic_statement

denotes

In the next step we will check for characteristics of HCWs that may predispose for an increased pathogen spread to patients.

T418

256551-256657

Epistemic_statement

denotes

We propose that humoral memory, acquired during colonization, shapes the response to S. aureus bacteremia.

T419

257313-257369

Epistemic_statement

denotes

This observation may be exploited for earlier diagnosis.

T420

258186-258332

Epistemic_statement

denotes

Interestingly, the clinical isolates inducing furunculosis frequently harbour the pvl-genes, encoding the toxin Panton-Valentine-Leukocidin (PVL).

T421

258660-258832

Epistemic_statement

denotes

To test whether invasive S. aureus strains that cause chronic furunculosis differ from colonizing strains we investigated their ability to induce cell death in neutrophils.

T422

259748-259829

Epistemic_statement

denotes

We can exclude indirect effects by modulating cytokines of contaminating T cells.

T423

260038-260147

Epistemic_statement

denotes

However, there were no differences between S. aureus cells from colonizing or furunculosis inducing isolates.

T424

260773-260829

Epistemic_statement

denotes

Schmidt 1 1 ZMBE, Infektiologie, Münster, Deutschland 2

T425

260830-260954

Epistemic_statement

denotes

Cell-penetrating proteins (CPP) are able to cross cellular membranes, either alone or in association with a bioactive cargo.

T426

261910-261982

Epistemic_statement

denotes

Free YopM could be detected throughout the cytoplasm and in the nucleus.

T427

262742-262768

Epistemic_statement

denotes

Horn 2 , M. Lindemann 2 1

T428

262769-262963

Epistemic_statement

denotes

Introduction: Vaccination against Streptococcus pneumoniae is recommended by the German advisory board for vaccination (STIKO) in immunocompromized patients such as kidney transplant recipients.

T429

262964-263065

Epistemic_statement

denotes

S. pneumoniae mainly infects the upper respiratory tract; it can cause lobar pneumonia or meningitis.

T430

263140-263276

Epistemic_statement

denotes

It was the aim of the present study to define the long-term efficiency of vaccination in clinically stable kidney transplant recipients.

T431

264489-264651

Epistemic_statement

denotes

Conclusion: Our results demonstrate that kidney transplant recipients can produce almost normal concentrations of antibodies against pneumococcal polysaccharides.

T432

265380-265531

Epistemic_statement

denotes

However, the activation of CD95 further increases pulmonary ceramide levelsand results in a vicious cycle of CD95 activation and ceramide accumulation.

T433

265852-266016

Epistemic_statement

denotes

These findings identify CD95 as an important regulator of lung functionsin cystic fibrosis and suggest that CD95 may be a novel target for treating cystic fibrosis.

T434

266305-266394

Epistemic_statement

denotes

The adaptive immune system can mobilize different effector mechanisms to a given antigen.

T435

269305-269396

Epistemic_statement

denotes

It appears that the cleavage of MyD88 uncouples the activation of TLR4 from NF-B signaling.

T436

269397-269528

Epistemic_statement

denotes

Thus, the disruption of MyD88 signaling in the execution of apoptosis may render the dying cells less sensitive to TLR stimulation.

T437

269529-269704

Epistemic_statement

denotes

This suggests that the cleavage of MyD88 is implicated in apoptotic death signaling by conferring immunogenic tolerance to the dying cell in response to microbial stimulation.

T438

269874-270002

Epistemic_statement

denotes

A crucial step in host colonization is the adhesin-mediated binding of this pathogen to the cells of the respiratory epithelium.

T439

270003-270199

Epistemic_statement

denotes

For cytadherence M. pneumoniae exhibits a complex membrane extension called attachment organelle which includes amongst other proteins the major adhesin P1 and the adherenceassociated protein P30.

T440

270887-271075

Epistemic_statement

denotes

We used this chimeric protein as antigen for an immunization strategy to elicit an antibody response in the respiratory tract of guinea pigs which can reduce the adhesion of M. pneumoniae.

T441

271737-271998

Epistemic_statement

denotes

The results are promising to achieve increased levels of M. pneumoniae-specific secretory IgA in comparison to the conventional systemic immunization by using the advantages of chitosan for the nasal vaccination of host organisms with the characterized antigen.

T442

272711-272793

Epistemic_statement

denotes

Two fibrinogen binding adhesins have been previously described for S. lugdunensis.

T443

272963-273043

Epistemic_statement

denotes

To date a fibronectin binding protein for S. lugdunensis has not been described.

T444

273044-273236

Epistemic_statement

denotes

We sought to investigate whether S. lugdunensis is internalized into the epithelial and endothelial cell line cells (5637 and EA.hy 926) using a previously described FACS-based invasion assay.

T445

273237-273402

Epistemic_statement

denotes

We could show that clinical isolates of S. lugdunensis were internalized into human urinary bladder carcinoma cell line 5637 and the endothelial cell line EA.hy 926.

T446

273403-273515

Epistemic_statement

denotes

Interestingly, all strains that invade into human urinary bladder carcinoma cell line 5637 bound to fibronectin.

T447

273800-274020

Epistemic_statement

denotes

The discovery of the internalization attribute of S. lugdunensis and its linkage to fibronectin binding suggests that the internalization of this important pathogen also occurs via a fibronectin mediated surface contact.

T448

274021-274293

Epistemic_statement

denotes

J. Elias* 1 , A. Tremmel 1 , U. Vogel 1 1 Universität Würzburg, Institut für Hygiene und Mikrobiologie, Würzburg, Deutschland Laboratory staff working with Neisseria meningitidis should be offered immunization with available vaccines against serogroups A, C, W-135, and Y.

T449

274294-274690

Epistemic_statement

denotes

As part of our biological safety management we have performed a crosssectional study with 20 individuals between 18 and 50 years, who were vaccinated once with quadrivalent polysaccharide vaccine; the aims of the study were: estimation of the duration of protection by polysaccharide vaccine; and assessment whether revaccination with newly available quadrivalent conjugate vaccine was necessary.

T450

275506-275580

Epistemic_statement

denotes

Mean protective duration, however, exceeded 100 months for all serogroups.

T451

275737-275864

Epistemic_statement

denotes

In conclusion, our analyses might point to less effective immunization against serogroup W135 by a polysaccharide-only vaccine.

T452

277143-277238

Epistemic_statement

denotes

The zymogen plasminogen can be converted by specific activators to the serine protease plasmin.

T453

278608-278794

Epistemic_statement

denotes

A20, an ubiquitin-editing enzyme, can block the proximal NF-B signalling pathway under various stimulations and A20 knockout mice succumb prematurely from uncontrolled hyperinflammation.

T454

280174-280314

Epistemic_statement

denotes

Interestingly, mRNA levels of iNOS, which is responsible for producing anti-malarial NO, were also significantly higher in infected KO mice.

T455

280315-280508

Epistemic_statement

denotes

Our study demonstrates that A20 deletion in hepatocytes is beneficial for parasite clearance during malaria liver stage infection, presumably by inducing a stronger local inflammatory response.

T456

280509-280616

Epistemic_statement

denotes

Augmenting anti-liver stage defense mechanisms may further improve experimental malaria vaccine strategies.

T457

281020-281100

Epistemic_statement

denotes

It has been shown that Mycobacteria infect their host by various mechanisms, eg.

T458

281224-281453

Epistemic_statement

denotes

Our group has found a lipid (Phenolic glycolipid, PGL) in the outer cell wall of Mycobacterium marinum (Mmar, a model organism for the research of Mtb) which might interfere with the innate immune system (Robinson et al., 2008) .

T459

281454-281561

Epistemic_statement

denotes

We are currently focused on establishing the link between PGL and the pathways of the innate immune system.

T460

282755-282881

Epistemic_statement

denotes

Discussion: Our findings suggest that PGL is indeed able to interfere with the signaling pathways of the innate immune system.

T461

282882-283007

Epistemic_statement

denotes

We could show that PGL supresses the production of IL-6, IL-12p40 and TNF-a RNA in HMDM after stimulation with HK-BCG or LPS.

T462

283129-283203

Epistemic_statement

denotes

It still remains elusive where exactly PGL interferes with these pathways.

T463

283320-283418

Epistemic_statement

denotes

Our work could therefore help to complete the picture of the infection mechanisms of Mycobacteria.

T464

283419-283559

Epistemic_statement

denotes

The intracellular protozoan parasite Toxoplasma gondii can invade the brain and cause a persistent infection, toxoplasmic encephalitis (TE).

T465

283560-283697

Epistemic_statement

denotes

IFNproducing CD8 + T cells, activated microglia, macrophages, and astrocytes appear to be the major effector mechanisms in host immunity.

T466

284099-284153

Epistemic_statement

denotes

Little is known about the role of ADAP in brain cells.

T467

284154-284369

Epistemic_statement

denotes

Since we could demonstrate that ADAP-deficient (ADAP -/-) mice showed ameliorated disease progression in the experimental autoimmune encephalomyelitis (EAE) model, a function of ADAP in brain cells was hypothesized.

T468

284841-285019

Epistemic_statement

denotes

Although the number of IFN-producing lymphocytes was increased in the brains of ADAP -/mice, all ADAP -/mice died until 54 days post infection, while all wild-type mice survived.

T469

285129-285350

Epistemic_statement

denotes

These data indicate an important role of ADAP for the activation of microglia cells during toxoplasmosis, whereas the integrin-mediated migration of T cells through the blood-brain-barrier seems to be independent of ADAP.

T470

285616-285641

Epistemic_statement

denotes

Zipfel 1,2 , C. Skerka 1

T471

285642-285779

Epistemic_statement

denotes

Staphylococcus aureus is a human pathogen that lives as a human commensal but can also cause superficial and life-threatening infections.

T472

287505-287710

Epistemic_statement

denotes

Although IFN-l has been shown to predominantly act on mucosal organs such as the lung and gastrointestinal tract, studies using IFN-l receptor-deficient mice have failed to define a non-redundant function.

T473

288087-288344

Epistemic_statement

denotes

Quantitative RT-PCR and simultaneous immunostaining of virus-infected cells and the antiviral Mx1 protein highlighted the distinct responsiveness of intestinal epithelial cells to IFN-l and its critical role to restrict epithelial viral replication in vivo.

T474

288684-288837

Epistemic_statement

denotes

This defence mechanism works very efficiently despite the often low number of pathogens and the limited amount of mediators secreted per epithelial cell.

T475

289167-289365

Epistemic_statement

denotes

Cell-to-cell communication was independent of gap junction formation, cytokine secretion, ion fluxes or nitric oxide synthesis, but required NADPH oxidase (Nox) 4-dependent oxygen radical formation.

T476

290011-290125

Epistemic_statement

denotes

However, tryptophan metabolites produced in the kynurenine pathway are able to inhibit the growth of immune cells.

T477

290643-290774

Epistemic_statement

denotes

Detailed analyses indicate that this antiparasitic effect is due to a toxic effect of the tryptophan metabolites on the host cells.

T478

291108-291182

Epistemic_statement

denotes

Quantitative analysis of the toxicity indicates that some tumor cells e.g.

T479

291369-291585

Epistemic_statement

denotes

These metabolites might inhibit the activity of tumor specific T-cells, while the enhanced resistance of some tumor cells against the toxic effect of tryptophan metabolites might represent an immune escape mechanism.

T480

291586-291769

Epistemic_statement

denotes

Background: Fibroblasts regulate epithelial cell differentiation, are responsible for wound healing, control inflammation process and seem to play an important role in cancerogenesis.

T481

291914-291966

Epistemic_statement

denotes

The linkage might be the hyaluronan (HA) metabolism.

T482

291967-292109

Epistemic_statement

denotes

Bacteria produce hyaluronidases and bacterial products interact with Toll-like-receptors (TLRs) which also seem to be linked to HA metabolism.

T483

292110-292250

Epistemic_statement

denotes

We investigated how far microorganisms/microbial products influence the metabolism of HA in human dermal fibroblasts through TLR activation.

T484

293475-293573

Epistemic_statement

denotes

However, all microorganisms and the microbial products under study did not modulate HA metabolism.

T485

293835-293933

Epistemic_statement

denotes

However, a possible role of HA metabolism in host-microorganism interacting needs further studies.

T486

294738-294898

Epistemic_statement

denotes

As to date, a constitutive expressed specific unique marker for human Treg cells is not available, an exact quantification on protein or RNA level is imprecise.

T487

295964-296064

Epistemic_statement

denotes

Heterologous antigens can be expressed in Salmonella as fusions with recombinant or native proteins.

T488

296065-296311

Epistemic_statement

denotes

This approach has been used mainly to direct the expression of the desired antigen to a particular location of the bacterial cell and to increase the immunogenicity of foreign antigens by fusing them to proteins that could exert a carrier effect.

T489

296312-296522

Epistemic_statement

denotes

The type III secretion system (T3SS)-mediated translocation by Salmonella can be used for efficient delivery of heterologous antigens into the cytosol of APC, leading to stimulation of both CD4 and CD8 T-cells.

T490

296649-296734

Epistemic_statement

denotes

These effectors proteins are associated with endosomal membranes after translocation.

T491

297136-297414

Epistemic_statement

denotes

By comparison of various attenuated carrier strains, we observed that the htrA/purD double mutant strain can be used efficiently as attenuated carrier for vaccination and observed the efficient stimulation invitro T-cell proliferation by the delta sifA mutant strain as carrier.

T492

297642-297810

Epistemic_statement

denotes

Differential expression and inducibility of Dusp gene expression suggest that these phosphatases specify the outcome of MAPK activation in terms of cytokine production.

T493

298411-298546

Epistemic_statement

denotes

However, embryonic development of homozygous mice was grossly normal until E18.5, indicating that Dusp16trap/trap mice die perinatally.

T494

299359-299490

Epistemic_statement

denotes

The cellular response of human monocyte derived macrophages to infection with genetically distinct M. tuberculosis complex strains

T495

299491-299754

Epistemic_statement

denotes

Aim of the study: The Mycobacterium tuberculosis complex (MTBC) was initially regarded as a highly homogeneous population; however, recent data suggest the causative agents of tuberculosis are genetically and functionally more diverse than appreciated previously.

T496

299755-299877

Epistemic_statement

denotes

The impact of this natural variation on the virulence of the pathogen and clinical manifestations remains largely unknown.

T497

300757-300936

Epistemic_statement

denotes

However, additional data also demonstrate that a particular MTBC genotype translates into a distinct biological response profile when getting into contact with human immune cells.

T498

301693-301786

Epistemic_statement

denotes

Nuclear localization was due to a so far unknown bipartite nuclear localization signal (NLS).

T499

302529-302627

Epistemic_statement

denotes

Limitation of p65 availability resulted in reduced expression of a subset of NFkB dependent genes.

T500

303597-303734

Epistemic_statement

denotes

How these unique transcriptional responses are generated, and which role they play for Th1 and Th17 induction is incompletely understood.

T501

303920-304023

Epistemic_statement

denotes

However, little is known about the TF profile induced downstream of these constitutively expressed TFs.

T502

305610-305722

Epistemic_statement

denotes

Specifically IFIT2 may recognize and may prevent translation of capped viral mRNA lacking 2'-O methylation [3] .

T503

305723-306010

Epistemic_statement

denotes

Stimulation of interferon / Receptor (IFNAR) -/bone marrow derived macrophages (BMDM) demonstrates that TLR3 and TLR4 ligands as well IFN-induced IFIT-2 protein expression is type I interferon receptor dependent, indicating that IFIT-2 can be directly induced by type I interferons only.

T504

306190-306322

Epistemic_statement

denotes

In order to investigate a potential role of IFIT-2 in inflammatory responses, IFIT-2 -/and IFIT-2 +/+ BMDM were stimulated with LPS.

T505

306323-306527

Epistemic_statement

denotes

IFIT-2 -/-BMDM show significantly reduced TNF-, IL-6, MCP-1 and MIP-2 secretion, indicating that IFIT-2 contributes to type I interferon mediated amplification of the LPS induced proinflammatory response.

T506

306528-306695

Epistemic_statement

denotes

In line with these findings, it could be demonstrated that IFIT-2 -/mice are less susceptible to LPS mediated endotoxin shock compared to littermate wildtype controls.

T507

307101-307231

Epistemic_statement

denotes

Evidence is accumulating which implies that coagulation can also contribute to the early innate immune response against pathogens.

T508

307232-307369

Epistemic_statement

denotes

Activation of the intrinsic pathway of coagulation, also known as the contact system, seems to play an important role in these processes.

T509

307370-307558

Epistemic_statement

denotes

Previous work has shown that it can be activated on the surface of many pathogenic bacterial species, which in turn leads to the generation of antimicrobial peptides and bacterial killing.

T510

308330-308434

Epistemic_statement

denotes

However, in infected fXIII -/animals, bacteria were widespread and scattered over a large affected area.

T511

309693-309901

Epistemic_statement

denotes

Given the high expression of LPLA2 in macrophages and its importance in membrane homeostasis and phospholipid turnover, we hypothesized that LPLA2 contributes to host responses against intracellular bacteria.

T512

311186-311374

Epistemic_statement

denotes

Taken together, our data indicate that LPLA2 is involved in the clearance of bacteria by macrophages and the processing of bacterial antigens for subsequent generation of T cell responses.

T513

311375-311681

Epistemic_statement

denotes

Though (IL)-17A/F-producing T helper (TH)17 cells are potent inducers of tissue inflammation and have been associated with several chronic and autoimmune inflammatory diseases, the main function of TH17 cells appears to be the clearance of pathogens, which are not appropriate affected by TH1 or TH2 cells.

T514

311947-312135

Epistemic_statement

denotes

Interestingly, Mtb-infected IL-17A -/mice efficiently generated interferon-gamma (IFNgamma)-producing TH1 cells and IFNgammadependent effector responses after low dose (100 CFU) infection.

T515

312136-312361

Epistemic_statement

denotes

However, IL-17A -/mice were not able to control mycobacterial replication during the chronic phase of experimental TB after low dose infection and died earlier (200 days post infection (dpi)) than corresponding wildtype mice.

T516

312486-312689

Epistemic_statement

denotes

The breakdown of controlling mycobacterial replication after low and high dose infection was associated with a modulation of gene expression of pro-inflammatory cytokines, chemokines and their receptors.

T517

312690-312898

Epistemic_statement

denotes

Especially the highly increased gene expression of IL-17F in IL-17A -/mice lead to the hypothesis that hypercompensation of IL-17A deficiency by IL-17F induce neutrophilia and susceptibility to Mtb infection.

T518

313163-313245

Epistemic_statement

denotes

Hence, IL-17A appears to play no direct role for protection against Mtb infection.

T519

313246-313507

Epistemic_statement

denotes

(Supported by the Inflammation Research Excellence Cluster) Staphylococcus (S.) aureus is a frequent cause of severe skin and soft tissue infections in humans, the treatment of which is complicated by the emergence of multi-resistant and hyper-virulent strains.

T520

314333-314443

Epistemic_statement

denotes

Surprisingly, the direct encounter of bacterial cells by PMN did not always lead to an uptake of the pathogen.

T521

314960-315067

Epistemic_statement

denotes

Here, we observed that Agr activity could be localized to small areas at the margin of the infection focus.

T522

317845-318027

Epistemic_statement

denotes

Our observation that neutralisation of CYLD in WT mice by siRNA partially protected WT mice from lethal listerioses identifies CYLD as a potential therapeutic target in listerioisis.

T523

318733-318853

Epistemic_statement

denotes

Surprisingly, following a phase of partial protection, all complement factor C3 -/mice died until day 17 post infection.

T524

319480-319653

Epistemic_statement

denotes

In summary: Our data indicate that C3-effector functions are harmful early in C. psittaci infection; increased Chlamydia uptake mediated by C3b might be the reason for that.

T525

319654-319845

Epistemic_statement

denotes

However, later in infection, when specific immunity becomes essential for defence, complement activation seems to be necessary for the fine-tuning of an otherwise deleterious immune response.

T526

320316-320461

Epistemic_statement

denotes

In order to cross the first line of host innate immune defence, P. aeruginosa has developed multiple strategies to escape host complement attack.

T527

320462-320633

Epistemic_statement

denotes

Complement resistance is crucial for bacterial virulence and several pathogens acquire host complement inhibitors such as vitronectin and Factor H to modulate this attack.

T528

321645-321821

Epistemic_statement

denotes

Lpd bound vitronectin in a dose-dependent manner and heparin inhibited the Lpd/vitronectin binding, suggesting that Lpd binds one of the heparin binding domains of vitronectin.

T529

322728-323041

Epistemic_statement

denotes

Further Yersinia is expected to release typical pathogen-associated molecular patterns (PAMPs) such as lipopolysaccharide (LPS), peptidoglycan fragments (PG), lipoprotein (LP) and the Yersinia V antigen (LcrV), which are recognized by the respective host receptors (PRRs) such as diverse TLRs or NOD1/2 receptors.

T530

323042-323239

Epistemic_statement

denotes

PRR signaling leads to release of pro-inflammatory cytokines (TNF, IL-6) as the first step in host defense activation followed by an antiinflammatory response such as secretion of IL-10 and IL-1Ra.

T531

323240-323510

Epistemic_statement

denotes

From this, we suggest that the infection process can be separated in two different modes of pathogen -host cell communication: short-distance effect = silencing of contacted cells and long-distance effect = release of PAMPs with recruitment and activation of phagocytes.

T532

323511-323798

Epistemic_statement

denotes

With the aim to unravel which PAMP-receptor is involved in control of Yersinia-infection, we used different ko-mice with defined defects in innate immunity (TLRs-und NODs -signaling pathway and defects in IL-10 and IL1-Ra production) for susceptibility testing towards Y. enterocolitica.

T533

324527-324724

Epistemic_statement

denotes

Further more, we obtained evidence that Yersinia susceptibility of mice is closely associated with dynamics of neutrophil recruitment to the site of infection due to host cell chemokine production.

T534

325158-325566

Epistemic_statement

denotes

Peptides derived from virulence factor of E.coli inhibit TLR signaling and are new promising candidates for treatment of autoimmune diseases and sepsis F. Roemmler* 1 , C. Cirl 1 , T. Miethke 1 1 Technical University Munich, Institute of Medical Microbiology, Immunology and Hygiene, München, Deutschland Toll like receptor signaling is known to be part of the first line defense of the innate immune system.

T535

326223-326311

Epistemic_statement

denotes

cyclophosphamide), which are limited in their efficiency and cause immense side effects.

T536

327125-327251

Epistemic_statement

denotes

Moreover, peptides show promising effects in a murine LPS shock-model leading to significantly reduced TNF-alpha serum levels.

T537

327252-327444

Epistemic_statement

denotes

In conclusion, the TcpC-derived peptides are able to inhibit TLR signaling without showing any side effects and are promising candidates for new therapeutics in autoimmune diseases and sepsis.

T538

328246-328352

Epistemic_statement

denotes

However, little is known about their direct interaction with fungi, especially with Aspergillus fumigatus.

T539

329588-329715

Epistemic_statement

denotes

We could also observe defined patterns of gene induction, especially regarding cytokine and chemokine gene expression profiles.

T540

329716-329786

Epistemic_statement

denotes

By multiplex ELISA assays gene expression patterns could be confirmed.

T541

330075-330271

Epistemic_statement

denotes

The course of Plasmodium yoelii-infection is affected by CD4 + Foxp3 + regulatory T-cells Regulatory T-cells (Tregs) play a critical role in the control of a variety of different immune responses.

T542

330272-330385

Epistemic_statement

denotes

However, studies on the impact of Tregs during the course of Plasmodium-infection have shown conflicting results.

T543

331288-331547

Epistemic_statement

denotes

Interestingly, P. yoelii-infection of CD4IL10-KO mice leads to a reduced suppressive capability of CD4 + CD25 + Tregs and a significant enhanced inflammatory CD8 + T-cell response compared to WT mice, whereas the parasitic burden is only marginallyl affected.

T544

331907-332134

Epistemic_statement

denotes

However, when a T helper (Th)1-based immune response develops, interferon (IFN)-gammaactivated macrophages are the primary immune cells that control T. cruzi replication by the production of reactive nitric intermediates (RNI).

T545

332374-332450

Epistemic_statement

denotes

However, this susceptibility was not due to an impaired Th1 immune response.

T546

333292-333470

Epistemic_statement

denotes

Taken together, our results suggest that the IL-23-IL-17A-axis is necessary for host protection against T. cruzi infection by stimulating antimicrobial mechanisms in macrophages.

T547

333739-333953

Epistemic_statement

denotes

We investigated the potential anti-inflammatory and immunomodulatory mechanisms of the above mentioned compounds in a murine model of hyper-acute Th1-type ileitis following peroral infection with Toxoplasma gondii.

T548

335532-335654

Epistemic_statement

denotes

These findings provide novel and potential prophylaxis and treatment options of patients with inflammatory bowel diseases.

T549

336145-336441

Epistemic_statement

denotes

As sepsis is one of the major causes of mortality that is partly due to an exaggerated pro-inflammatory immune response (3), we tested whether natural infection with the rodent filarial nematode Litomosoides sigmodontis ameliorates a systemic inflammatory immune response that is induced via i.p.

T550

336678-336978

Epistemic_statement

denotes

This correlated with significantly increased amounts of peritoneal bioactive TGF and IL-10 in infected mice compared to uninfected controls, whereas levels of the proinflammatory cytokines IL-6, IL-1 , IFN , and MIP2 were not decreased, rather trended to be increased in L. sigmodontis infected mice.

T551

336979-337180

Epistemic_statement

denotes

Similarly, increased expression of CD80 and CD86 on peritoneal macrophages and neutrophils suggest a stronger activation of these cell types in L. sigmodontis infected mice 6 hours after LPS challenge.

T552

337269-337463

Epistemic_statement

denotes

As L. sigmodontis infected animals had a stronger initial pro-inflammatory immune response, we evaluated whether challenge with vital E. coli may be more efficiently controlled in infected mice.

T553

337720-338043

Epistemic_statement

denotes

Our results suggest that L. sigmodontis induced modulation of the immune response may increase the survival rate after bacterial challenge by inducing a strong pro-inflammatory immune response that controls bacteremia, followed by a potent anti-inflammatory mechanism that reduces pathology due to exaggerated inflammation.

T554

338044-338149

Epistemic_statement

denotes

Introduction: Effective therapy is vital in reducing mortality of Pneumocystis jirovecii pneumonia (PCP).

T555

338670-338813

Epistemic_statement

denotes

However, at the moment nothing is known about its usefulness for monitoring the patient's clinical course or for identifying treatment failure.

T556

338814-338976

Epistemic_statement

denotes

Methods: We conducted a retrospective case control study to investigate whether consecutive serum BG-measurements can be used to assess treatment response in PCP.

T557

340021-340161

Epistemic_statement

denotes

Separate analysis of the different subgroups showed that decreasing BG-levels are associated with a favourable outcome in 88% of cases (Fig.

T558

340306-340480

Epistemic_statement

denotes

One patient with a complex BG-kinetic had a clinically, radiologically and microbiologically proven treatment failure and his BG level increased 7 fold at the same time (Fig.

T559

340486-340586

Epistemic_statement

denotes

Conclusion: Decreasing BG-levels show a good correlation (88%) with a favourable treatment response.

T560

340587-340695

Epistemic_statement

denotes

This may assist in deciding whether to continue first-line therapy in cases of missing clinical improvement.

T561

340696-340801

Epistemic_statement

denotes

Under special circumstances, consecutive BG-measurements might be suitable to identify treatment failure.

T562

340802-340952

Epistemic_statement

denotes

However, the overall correlation of increasing BG-levels with an adverse outcome is poor (44%) and its usefulness for follow-up in severe PCP limited.

T563

343448-343688

Epistemic_statement

denotes

The results of the genotypic and phenotypic characterization of the MRSA collection analyzed here will be compared with those of matched controls of patients of the same risk-factors colonized with methicillin-susceptible S. aureus strains.

T564

343689-343866

Epistemic_statement

denotes

Backround: Rapid detection of causative microorganisms in patients with bloodstream infections is crucial for the early initiation or adaption of adequate antimicrobial therapy.

T565

343867-344118

Epistemic_statement

denotes

Objective: The goal of this prospective study was to evaluate a commercial PCR-based kit (SeptiFast, SF) for the detection of 25 clinically important pathogens in septic patients after liver transplantation (LTX) and major abdominal surgery (non-LTX).

T566

345084-345313

Epistemic_statement

denotes

Objective: There is growing evidence that microgaps between dental implants and their abutments lead to bacterial contamination of the interior of the implants that might provide a reservoir for pathogens causing periimplantitis.

T567

345314-345484

Epistemic_statement

denotes

The aim of this study was to investigate the intraimplant bacterial spectrum of two stage implants, and to compare the results of two different sample collection methods.

T568

346713-346901

Epistemic_statement

denotes

Most taxa per implant found were detected by brush collection (median: 62 % of species), however, only combination of both methods allowed complete analysis of the intra-implant microbiom.

T569

346902-347053

Epistemic_statement

denotes

Conclusions: Our results suggest ubiquitous heavy contamination of internal spaces of dental implants, revealing a broad spectrum of bacterial species.

T570

347054-347263

Epistemic_statement

denotes

For analysis of the intra-implant microflora the combined examination of both intra-implant fluid and cavity surface samples is recommended in order to cover biofilm-grown as well as planktonic microorganisms.

T571

347780-347992

Epistemic_statement

denotes

Although we do not have detailed knowledge about genomic alterations, S. aureus long-time persistence in the CF lung assumedly selects for phenotypes that are tightly adapted to this specific environmental niche.

T572

348401-348723

Epistemic_statement

denotes

By Sanger sequencing we could confirm mutations in a number of genes that are associated with virulence or antibiotic resistance, such as protein A (spa), the autoinducer sensor kinase (agrC), the allelic variants of bone sialoprotein-binding protein (bbp/sdrE), and DNA topoisomerases type II and IV (gyrA and parC/grlA).

T573

348724-348833

Epistemic_statement

denotes

All of these mutations are associated with amino acid changes and we currently analyze the potential outcome.

T574

348834-349021

Epistemic_statement

denotes

The altered gyrA corresponds to an acquired resistance towards fluoroquinolones, whereas altered agrC is assumedly associated with different characteristics affecting S. aureus virulence.

T575

349145-349286

Epistemic_statement

denotes

Our preliminary data suggest that adaptation of persistent CF isolates include changes on DNA level and the regulation of protein expression.

T576

349287-349425

Epistemic_statement

denotes

However, detected mutations did not occur in all patients indicating that the host environment promotes individual adaptational processes.

T577

349426-349558

Epistemic_statement

denotes

Resulting altered virulence may favor precise camouflage in response to the hostile environment under a specific clinical situation.

T578

349559-349693

Epistemic_statement

denotes

Our results may help to understand the complex pathogenesis of chronic infection against the background of host-pathogen interactions.

T579

349694-349833

Epistemic_statement

denotes

Staphylococcus pettenkoferi is a coagulase-negative staphylococcus (CNS) that has been recently described as a rarely isolated new species.

T580

349834-349932

Epistemic_statement

denotes

Whether this new species is a harmful pathogen or an harmless bystander could not be answered yet.

T581

349933-350012

Epistemic_statement

denotes

Nevertheless, a few case reports suggested an invasive role of S. pettenkoferi.

T582

350013-350143

Epistemic_statement

denotes

Staphylococcus lugdunensis and S. pettenkoferi have been described as potentially related species as shown by biochemical methods.

T583

350144-350333

Epistemic_statement

denotes

To determine whether this new species could be a putative pathogen similar to S. lugdunensis, the strains were characterized for the presence of fibrinogen and fibronectin binding adhesins.

T584

350982-351211

Epistemic_statement

denotes

The lack of fibrinogen and fibronectin binding adhesins, and the lack of an internalization ability indicate that S. pettenkoferi is more likely a harmless colonizer of the human skin flora more than a harmful infective pathogen.

T585

351462-351611

Epistemic_statement

denotes

Systemic dissemination of Cpn from the lung to peripheral organs and arteric vessels has been shown to be mediated by blood mononuclear cells (PBMC).

T586

351742-351907

Epistemic_statement

denotes

It has been shown previously that intracellular morphology and growth characteristics of chlamydiae signficantly differ between human monocytes and epithelial cells.

T587

351908-352025

Epistemic_statement

denotes

However, phenotypic differences between isolates from different anatomical origins have not been investigated so far.

T588

352980-353288

Epistemic_statement

denotes

Conclusion/Discussion: Clinical isolates of Cpn from the bood circulation (PBMC, coronary arteries) can be differentiated from lung isolates by nonsynonymous SNPs in 9 ORFs related with chlamydial metabolisms, bacterial transition, inclusion membrane formation, LPS synthesis and regulation of sigma factors.

T589

353289-353482

Epistemic_statement

denotes

Further studies will have to show whether these genetic differences are responsible for the observed phenotypic differences between the isolates with regard to intracellular growth and progeny.

T590

353483-353559

Epistemic_statement

denotes

Detection of carbapenemases has only very rarely been reported from Germany.

T591

353743-353944

Epistemic_statement

denotes

VIM-1, VIM-2 and KPC-2 were detected in diverse enterobacterial species and Pseudomonas aeruginosa isolates suggesting a more widespread prevalence of carbapenemases in Germany than currently believed.

T592

354518-354621

Epistemic_statement

denotes

One of the earliest pathogens which can be isolated from lungs of CF patients is Staphylococcus aureus.

T593

354806-355007

Epistemic_statement

denotes

This project is aiming to further reveal the mechanisms underlying the adaptation of S. aureus during persistent colonization and infection to the hostile niche of CF patients using proteomic analysis.

T594

355008-355096

Epistemic_statement

denotes

In addition the virulence potential was assessed in in vitro, as well as in vivo assays.

T595

355504-355629

Epistemic_statement

denotes

Virulence potential of the strains was investigated in vitro by means of invasion assays using the epithelial cell line A549.

T596

355630-355729

Epistemic_statement

denotes

Furthermore, the virulence potential was studied in vivo in a Caenorhabditis elegans killing assay.

T597

355730-355857

Epistemic_statement

denotes

Preliminary results of invasion assays revealed different alterations in invasive properties comparing early and late isolates.

T598

355858-356049

Epistemic_statement

denotes

For late isolates of two patients an increase of invasive properties compared to the early isolates could be observed whereas the properties of the late isolate of one patient were decreased.

T599

356522-356834

Epistemic_statement

denotes

Since adaptation of bacteria can occur on genomic as well as on regulatory levels, it is of importance to investigate the alterations in late isolates compared to early isolates in a proteomic approach which allows the analysis of differences in protein expression as well as of post-translational modifications.

T600

357679-357750

Epistemic_statement

denotes

Conclusion: Chronic infections with E. faecalis are difficult to treat.

T601

357899-358023

Epistemic_statement

denotes

The combination of vancomycin containig cement with systemic ampicillin therapy might be a useful option for these patients.

T602

358421-358567

Epistemic_statement

denotes

Similarity between the mycobacterial and the eukaryotic TrxR system is low, therefore it may be used as a novel drug target to fight tuberculosis.

T603

359460-359703

Epistemic_statement

denotes

Although several important UPEC virulence factors and their role during pathogenesis have been described, many UPEC isolates cannot be unambiguously distinguished from commensal E. coli based on the presence of UPEC virulence-associated genes.

T604

359987-360078

Epistemic_statement

denotes

plasmids, bacteriophages or pathogenicity islands and can thus be horizontally transferred.

T605

360266-360419

Epistemic_statement

denotes

Interestingly, about 10 % of these isolates carried one or more known IPEC virulence genes, sometimes in combination with classical UPEC virulence genes.

T606

360558-360680

Epistemic_statement

denotes

Notably, among the atypical urine E. coli isolates were strains carrying marker genes of enteroaggregative E. coli (EAEC).

T607

360802-360996

Epistemic_statement

denotes

Our results indicate that nosocomial UTI due to E. coli may be caused by a diverse group of E. coli variants, some of which represent IPEC or carry virulence properties of diarrheagenic E. coli.

T608

360997-361241

Epistemic_statement

denotes

The combination of typical ExPEC and IPEC virulence determinants also further supports the finding that E. coli exhibits a marked genome plasticity and that gene transfer may promote an evolutionary transition from IPEC to ExPEC -or vice versa.

T609

361242-361462

Epistemic_statement

denotes

The relatively high prevalence of EAEC marker genes among urine isolates also demonstrates the heterogeneity of this pathotype and raises the possibility that some EAEC strains may have the potential to be uropathogenic.

T610

361556-361862

Epistemic_statement

denotes

& Parasitol., Lagos, Nigeria 2 Uniklinik Magdeburg, IMMB, Magdeburg, Deutschland Background: We investigated the association between the prevalent extended-spectrum beta-lactamase and the genetic lineage of Escherichia coli from two tertiary hospitals in Lagos, Nigeria within a period of 8 months in 2009.

T611

362493-362545

Epistemic_statement

denotes

They were however, all sensitive to the carbapenems.

T612

362606-362812

Epistemic_statement

denotes

All the CTX-M-15 producers carried the insertion sequence ISEcpI which has recently been demonstrated to mobilize 3'-adjacent genes to transfer between DNA replicons and is involved in spread of such ESBLs.

T613

363515-363592

Epistemic_statement

denotes

The high diversity of STs is remarkable among the CTX-M-15 positive isolates.

T614

364155-364264

Epistemic_statement

denotes

Interestingly, the bacterial diversity in the human nose reaches from aerobic to strictly anaerobic bacteria.

T615

364405-364570

Epistemic_statement

denotes

In order to investigate if bacteriocin production might play a role during nasal colonisation we analysed the bacteriocin production of nasal Staphylococcus strains.

T616

364803-364951

Epistemic_statement

denotes

Transposon plasmids could be transformed into various strains and mutagenesis was performed to identify corresponding bacteriocinbiosynthetic genes.

T617

365186-365345

Epistemic_statement

denotes

One of these bacteriocins, produced by an S. epidermidis strain, could be characterized as a nukacin-like lantibiotic with activity against Micrococcos luteus.

T618

365346-365519

Epistemic_statement

denotes

Extending our knowledge about the various interactions between staphylococcal and other nasal species could be important for finding new effective anti-S. aureus strategies.

T619

365520-365884

Epistemic_statement

denotes

Humanisation of the murine anti-IsaA antibody -a potential target for an antibody-based therapy against multi-resistant Staphylococcus aureus strains B. Oesterreich* 1 1 Institut für Molekulare Infektionsbiologie, Universität Würzburg, Würzburg, Deutschland Background: The Gram-positive bacterium Staphylococcus aureus is the major cause of nosocomial infections.

T620

365885-366179

Epistemic_statement

denotes

In particular, diseases caused by methicillin-resistant S. aureus (MRSA) are associated with higher morbidity, mortality and medical costs due to showing resistance to several classes of established antibiotics and their ability to develop resistance mechanisms against new antibiotics rapidly.

T621

366180-366243

Epistemic_statement

denotes

Therefore, there is an urgent need for novel treatment options.

T622

366244-366360

Epistemic_statement

denotes

Immunotherapy has the potential to close the gap in the treatment of infections caused by multi-resistant S. aureus.

T623

368003-368136

Epistemic_statement

denotes

For an improved treatment of infectious diseases the identification of optimized combinations of antibiotics is a promising approach.

T624

370421-370572

Epistemic_statement

denotes

Consequently, the novel non-toxic (S)-2-aminoalkyl benzimidazoles represent promising candidates for future developments in antimycotic drug discovery.

T625

371206-371507

Epistemic_statement

denotes

As the interferon-gamma-release-assays (IGRA) have been shown to improve the diagnosis (better specificity and sensibility than TST) especially of latent tuberculosis infections (LTBI) this test has been increasingly requested with more than 8500 samples in 2010 by health care workers and clinicians.

T626

371727-371921

Epistemic_statement

denotes

These M. tuberculosis specific antigens (ESAT-6, CFP-10 und TB7.7) are lacking in all BCG strains and almost all non-tuberculous mycobacteria (NTM) except M. kansasii, M. szulgai and M. marinum.

T627

373685-373810

Epistemic_statement

denotes

For belgium isolates, 3 strains had a ST638 profile, 8 strains had ST543 profile and one strain had an unknown sequence type.

T628

374359-374636

Epistemic_statement

denotes

M. Höck* 1 1 DRK Kliniken Berlin / Westend, Institut für Mikrobiologie und Krankenhaushygiene, Berlin, Deutschland Objectives: ESBL producing E.coli strains have become a serious problem, as these strains often leave few therapeutic options, especially in intensive care units.

T629

374637-374674

Epistemic_statement

denotes

The therapeutic options seem limited.

T630

374899-375047

Epistemic_statement

denotes

The change for 2010 reads: Cephalosporin breakpoints for Enterobacteriaceae will detect clinically important resistance mechanisms (including ESBL).

T631

375048-375222

Epistemic_statement

denotes

Some strains that produce beta-lactamases are susceptible or intermediate to 3rd or 4th generation cephalosporins with these breakpoints and should be reported as found, i.e.

T632

377161-377213

Epistemic_statement

denotes

Three different strains could be clearly identified.

T633

377440-377489

Epistemic_statement

denotes

Patient B was probably an already prevalent case.

T634

377706-377844

Epistemic_statement

denotes

These results show great promise for MALDI-TOF mass spectrometry as an epidemiological tool for the real-time management of VRE outbreaks.

T635

377968-378059

Epistemic_statement

denotes

Conclusion: SAB is a common infection in German hospitals associated with a high mortality.

T636

379274-379699

Epistemic_statement

denotes

Last, but not least we provided the rationale for a treatment of the typical HUS with a complement inhibitory antibody: although it is well established that the released EHEC shiga toxins have a direct deleterious effect on kidney cells, they also activate complement and bind factor H, its main regulator, leading to both a stronger activation and a weaker control of complement (Orth et al., J Immunol 2009; 182:6394-400) .

T637

380446-380661

Epistemic_statement

denotes

Among the 77 microorganisms identified by multiplex-PCR, only 25 (32.5%) could be confirmed by blood culture, additional 17 could be confirmed by microbiological test results from other significant patient specimen.

T638

380662-380951

Epistemic_statement

denotes

Positive blood samples independent of the detection method were characterized by significant elevated levels of procalcitonin ( Infection with S. aureus can result in a clinical condition ranging from Systemic Inflammatory Response Syndrome to Septic Shock with multiple organ dysfunction.

T639

382474-382630

Epistemic_statement

denotes

These data indicate that membrane ceramide is an important mediator of immune system activation and pulmonary dysfunction in S. aureus induced septic shock.

T640

383098-383194

Epistemic_statement

denotes

In Pseudomonas aeruginosa resistance can be mediated by production of metallo--lactamases (MBL).

T641

385987-386100

Epistemic_statement

denotes

Biofilm formation on catheter or epithelial surfaces will further enhance the retention of these septic crystals.

T642

386239-386311

Epistemic_statement

denotes

However, due to severe side effects AHA has not been approved in Europe.

T643

386312-386447

Epistemic_statement

denotes

The purpose of this study was to test the urinary antiseptic and cation chelator nitroxoline (NIT) as a possible non-toxic alternative.

T644

387818-388005

Epistemic_statement

denotes

However, when biofilm was preformed in the presence of urea, the subsequent NIT effect on precipitate formation was lower, thus indicating an additional effect of NIT on urease induction.

T645

388269-388547

Epistemic_statement

denotes

Moreover, it was found to exhibit potent antimicrobial effects against all clinical isolates examined, and reduced precipitate formation in P. mirabilis biofilms, presumably by a combination of biofilm degradation, inhibition of urease induction and blockage of urease activity.

T646

390772-391051

Epistemic_statement

denotes

Cronobacter bacteria, formerly classified as Enterobacter sakazakii, have been implicated in several incidents as the cause of meningitis and enterocolitis with high mortality rates in premature infants resulting from feeding with contaminated powdered infant formula (PIF) [1] .

T647

391052-391205

Epistemic_statement

denotes

PIF therefore is strictly recommended to be "sakazakii-free" which is defined as the absence of any colony forming unit in 30 samples of 10g of PIF [2] .

T648

391829-391900

Epistemic_statement

denotes

Clean rooms are essential in aseptic pharmaceutical or food production.

T649

393281-393377

Epistemic_statement

denotes

Listeria may be spread through the fishprocessing equipment and machinery and may persist there.

T650

393378-393517

Epistemic_statement

denotes

Today, insufficient data exist whether the H1-lubricants applied in these machines are putative reservoirs and sources of L. monocytogenes.

T651

393682-393773

Epistemic_statement

denotes

In a first step, the presence of L. monocytogenes in the native H1-lubricants was assessed.

T652

394440-394559

Epistemic_statement

denotes

Interestingly, the isolate from smoked salmon tolerated this environment better than the reference and the type strain.

T653

394925-395066

Epistemic_statement

denotes

Outbreaks are rare, but in several of these cases contaminated powdered infant formula was identified as a source of C. sakazakii infections.

T654

396796-396911

Epistemic_statement

denotes

EHEC food-borne infections may lead to nonbloody diarrhea, bloody diarrhea and the hemolytic uremic syndrome (HUS).

T655

397133-397208

Epistemic_statement

denotes

Exposure to different environments may cause a shift in metabolic pathways.

T656

397209-397292

Epistemic_statement

denotes

In EHEC, this may also lead to a shift in the expression of virulence determinants.

T657

397863-397978

Epistemic_statement

denotes

In TSB, we found a high amount of the flagellin protein FliC, suggesting that it is downregulated in SIEM and SCEM.

T658

398458-398609

Epistemic_statement

denotes

The results of these analyses gave us a hint how environmental conditions affect the metabolism and virulence properties of EHEC O157:H7 strain EDL933.

T659

398938-399019

Epistemic_statement

denotes

Several species of Penicillium can grow in food that was given potassium sorbate.

T660

399301-399445

Epistemic_statement

denotes

The aim of this research is to know antifungal activity of lactic acid bacteria Lactobacillus plantarum 1BL-2 and TSD-10 against Penicillium sp.

T661

400005-400086

Epistemic_statement

denotes

this suggests that the antifungal activity not only because of acidic conditions.

T662

401390-401482

Epistemic_statement

denotes

Advantages and limitations of using MALDI-TOF technology for this application are discussed.

T663

401483-401645

Epistemic_statement

denotes

This study showed that fewer than 70% of frequently seen environmental isolates could be accurately identified with the MALDI Biotyper™ system (Bruker Daltonics).

T664

401646-401761

Epistemic_statement

denotes

The >30% that failed to be identified were largely due to limitations in the clinically focused Biotyper™ database.

T665

402804-403158

Epistemic_statement

denotes

Interestingly, PA possesses two isoenzymes of isocitrate dehydrogenase, namely dimeric Icd and the monomeric Idh that both catalyze the oxidative decarboxylation of isocitrate to ketoglutarate, CO2 and NAD(P)H. Beside PA, only very few bacteria have two isoenzymes of isocitrate dehydrogenase suggesting a role during adaptation to environmental changes.

T666

403975-404070

Epistemic_statement

denotes

Therefore, we will investigate these metabolic enzymes with a view to oxidative stress as well.

T667

404623-404875

Epistemic_statement

denotes

We could show that these genes are not translated as one protein, diminish the motility of the pathogen, alter the chemotactical behaviour of C. jejuni towards formic acid, but are not related to the utilization of formic acid by formate dehydrogenase.

T668

405911-406006

Epistemic_statement

denotes

The crucial step of all of these methods is the localization of the transposon insertion sites.

T669

406497-406584

Epistemic_statement

denotes

In the first step, the genomic DNA is cleaved with different restriction endonucleases.

T670

406944-407087

Epistemic_statement

denotes

Finally, using the derived fragment size pattern the most probable genomic position of the transposon can be calculated by the InFiRe software.

T671

407187-407288

Epistemic_statement

denotes

The method is potentially applicable to any virus or sequenced organisms with known genomic sequence.

T672

408067-408240

Epistemic_statement

denotes

Although the virulence of sigB deficient strains is often reported to be similar to that of wild type strains, the pathomechanism of different infection settings might vary.

T673

408241-408384

Epistemic_statement

denotes

Therefore, the rationale of this study was to investigate whether the deletion of sigB would lead to a different reaction of the infected host.

T674

408755-409054

Epistemic_statement

denotes

However, the results of this study did not provide any hints for differences in the pathomechanism of the S. aureus strains RN1HG Outer membrane vesicles are released from the outer membrane of pathogenic Neisseria and previous works suggested a role of OMVs in invasive meningococcal disease (IMD).

T675

409164-409344

Epistemic_statement

denotes

Because meningococcal OMV can be purified from plasma of IMD patients, we asked whether they impact polymorphonuclear neutrophils (PMN), which are a first line defence against IMD.

T676

409725-409821

Epistemic_statement

denotes

These results suggested reduced PMN mediated killing of Nm in the presence of meningococcal OMV.

T677

409822-410005

Epistemic_statement

denotes

As a possible causal effector protein we identified a ribosyl transferase that proved to be present in OMVs and whose knock-out reduced the above mentioned OMV effects on neutrophils.

T678

410163-410364

Epistemic_statement

denotes

This might aid the rapid spread of the bacteria once the blood vessels are invaded and thus support the rapid development of septic shock in many patients suffering from invasive meningococcal disease.

T679

411607-411862

Epistemic_statement

denotes

Inhibition of cortactin expression by siRNA silencing and mutation of critical amino acid residues within cortactin significantly reduced meningococcal invasion into brain endothelial cells indicating a critical role for cortactin in meningococcal uptake.

T680

412005-412242

Epistemic_statement

denotes

Together, these results indicate that N. meningitidis exploits the integrin signal pathway for its entry and that FAK is an important signalling molecule that mediates the transfer of signals from activated integrins to the cytoskeleton.

T681

412520-412734

Epistemic_statement

denotes

The fulminant septicemic course, named Waterhouse-Friderichsen syndrome, with massive hemorrhage into the adrenal glands and widespread petechial bleeding suggest pathophysiological inhibition of platelet function.

T682

413690-413811

Epistemic_statement

denotes

Our study provides evidence that NO plays an essential role in the pathophysiology of septicemic meningococcal infection.

T683

413812-413919

Epistemic_statement

denotes

Legionella pneumophila is a Gram-negative intracellular pathogen that can cause a severe form of pneumonia.

T684

414798-414974

Epistemic_statement

denotes

Zymography and enzyme assays demonstrate that OMVs display proteolytic and lipolytic activities which may contribute to the destruction of the alveolar lining during infection.

T685

414975-415095

Epistemic_statement

denotes

Confocal laser scanning microscopy revealed a spatial association between L. pneumophila OMVs and the host cell surface.

T686

415096-415200

Epistemic_statement

denotes

It remains unclear if this indicates adhesion, binding or fusion events between OMVs and host membranes.

T687

415201-415281

Epistemic_statement

denotes

The role of L. pneumophila OMVs in interbacterial communication is also unknown.

T688

415508-415648

Epistemic_statement

denotes

The presence of the L. pneumophila major outer membrane protein (MOMP) could not be detected in any of the target cells by Western blotting.

T689

415766-415909

Epistemic_statement

denotes

Ongoing studies address the effect of L. pneumophila OMVs on human macrophages in regard to metabolic activity and cytoskeleton rearrangements.

T690

416024-416132

Epistemic_statement

denotes

While B of S. aureus has been studied extensively, only little is known about the latter two sigma subunits.

T691

416451-416639

Epistemic_statement

denotes

In S. aureus, this alternative sigma factor seems to control a very small regulon, which includes the operons SA1374-SA1371, SA1418-SA1416, and the prophageencoded integrase gene int only.

T692

416640-416738

Epistemic_statement

denotes

However, nothing is known to date, whether and under which condition H is active in this pathogen.

T693

416739-416847

Epistemic_statement

denotes

To address this question we analyzed the expression of sigH and the Hdepended genes by different approaches.

T694

417157-417495

Epistemic_statement

denotes

Monitoring the luciferase activity of a S. aureus Newman strain harboring pTF9 during growth in TSB, however, failed to identify significant levels of luciferase activity or Gfp formation at nearly any growth stage analyzed, confirming previous findings indicating that H is essentially not active during growth under in vitro conditions.

T695

417907-418257

Epistemic_statement

denotes

Interestingly, neither the overexpression of sigH in strain Newman did allow to enhance the transcription of the int gene, nor did the inoculation of Newman and its sigH-derivative into fresh medium reveal clear differences in int transcription between the wild-type and the mutant, strongly suggesting that the int gene is not a direct target of H .

T696

418657-418799

Epistemic_statement

denotes

While chemotaxis and cytokine induction are crucial for infections, the molecular basis of the recognition by leucocytes has remained unknown.

T697

419285-419368

Epistemic_statement

denotes

Targeting FPR2 may help to manage severe infections induced by different pathogens.

T698

420452-420625

Epistemic_statement

denotes

Furthermore, 27 different SGG-isolates (10 5 -10 6 CFU/ml) were compared concerning the potential for stimulation the TNF--synthesis in whole blood during 4 h of incubation.

T699

421592-421726

Epistemic_statement

denotes

The comparison of the potential of different strains to stimulate TNF--synthesis in whole blood revealed significant differences (e.g.

T700

421808-421970

Epistemic_statement

denotes

Conclusions: SGG isolates revealed differences in the potential to stimulate IL-6, IL-8, MIP-1 and TNF-gene expression in both, endothelial cells and whole blood.

T701

421971-422062

Epistemic_statement

denotes

These divergences could affect the dimension and progress of endothelial cell damage in IE.

T702

424563-424791

Epistemic_statement

denotes

Interestingly, the amino acid sequences, which are crucial for plasminogen binding seem to vary with respect to localization within the glycolytic proteins and with respect to charge properties required for specific interaction.

T703

425830-425925

Epistemic_statement

denotes

However, the mechanism of pneumococcal endocytosis via the PspC-hpIgR interaction is not known.

T704

426307-426458

Epistemic_statement

denotes

Similar, the knock-down of dynamin by shRNA also impaired pneumococcal internalization suggesting that pneumococcal uptake requires functional dynamin.

T705

427087-427283

Epistemic_statement

denotes

In conclusion, the results suggest that pneumococci are internalized via the clathrin-mediated endocytic pathway and then sorted into different endosomal compartments of the epithelial host cells.

T706

427284-427379

Epistemic_statement

denotes

However, the intracellular fate after reaching the phago-lysosomes is still a matter of debate.

T707

427889-428144

Epistemic_statement

denotes

Because -toxin caused a state of energy crisis, starvation, and translational arrest, and because inhibition of PI3K prevented replenishment of cellular ATP, we further proposed that autophagy serves to maintain metabolic homeostasis in target cells (2) .

T708

428391-428547

Epistemic_statement

denotes

Interestingly, eIF2 -phosphorylation was triggered by -toxin with similar kinetics as in HaCaT cells, but the response was markedly sustained in Huh7 cells.

T709

428808-428971

Epistemic_statement

denotes

Since this effect was not due to a block of translation, sustained phosphorylation of eIF2 seems to promote killing of -toxintreated cells by an unusual mechanism.

T710

428972-429204

Epistemic_statement

denotes

Endothelial progenitor cells (EPCs) are a heterogeneous mixture of adult stem cells that play an essential role in revascularization after vascular damage and have shown promising results in regenerative therapy for ischemic injury.

T711

429205-429332

Epistemic_statement

denotes

In our work we investigated an unconventional method of improving the angiogenic potential of EPCs through bacterial infection.

T712

430232-430457

Epistemic_statement

denotes

Finally, when culture plates are coated with a basement membrane which simulates the extra-cellular matrix (Matrigel TM ), infected EPCs proliferate and assemble into complex, lumen containing vessel-like structures in vitro.

T713

430789-430944

Epistemic_statement

denotes

Cumulatively, our data demonstrate that infection with B. henselae can improve the angiogenic capacity of EPCs and even induce vessel-like growth in vitro.

T714

431148-431253

Epistemic_statement

denotes

In this study we want to show how YadA, Invasin and 1-integrins contribute to Yop translocation in vitro.

T715

431365-431483

Epistemic_statement

denotes

We will present evidence that (i) YadA and Invasin show striking differences how they contribute to Yop translocation.

T716

431484-431739

Epistemic_statement

denotes

(ii) For Invasin mediated Yop translocation an intact 1-integrin cytoplasmic domain and its connection to the actin cytoskeleton seems to be important in terms of the integrity of the whole receptor and its ability to perform high affinity ligand binding.

T717

431740-431896

Epistemic_statement

denotes

(iii) In contrast YadA does not require the 1-integrin cytoplasmic domain but might require additional factors beside integrins for effective Yop injection.

T718

433579-433803

Epistemic_statement

denotes

In conclusion, the data will show the individual impact of the thioredoxin-like proteins and their additive effect on resistance of pneumococci against oxidative stress, which is essential for invasive pneumococcal diseases.

T719

434689-434852

Epistemic_statement

denotes

A direct contribution to virulence has yet only been shown for the lipoprotein SlrA, which belongs to the family of peptidyl-prolyl cis/trans isomerases, and PpmA.

T720

434853-435066

Epistemic_statement

denotes

The role of other lipoproteins for pneumococcal colonization, virulence and transmission has not been systematically investigated although functional genomic analysis points towards their implication in virulence.

T721

435185-435325

Epistemic_statement

denotes

Hypothetical lipoproteins and lipoproteins with unknown function were selected to explore their role for pneumococcal fitness and virulence.

T722

436982-437102

Epistemic_statement

denotes

So far staphylococcal phages can be classified into 4 major sergroups A, B, D and F. They also differ in morphology e.g.

T723

437170-437320

Epistemic_statement

denotes

Interestingly electron micrograph images revealed that serogroup L phage 187, a phage only infecting strain L is a doubleganger of serogroup B phages.

T724

437912-438066

Epistemic_statement

denotes

To show that phage resistance is due to the loss of WTA phage susceptibility could be restored by complementation using a vector expressing the tagO gene.

T725

438067-438241

Epistemic_statement

denotes

Furthermore phage adsorption assays were performed to analyse if the observed phage resistance is due to the loss of the receptor or due to unknown post adsorption processes.

T726

438574-438712

Epistemic_statement

denotes

Furthermore the mutant produces lower amounts of biofilm so a possible role of L-type WTA in biofilm formation can not be excluded so far.

T727

438713-438845

Epistemic_statement

denotes

Taken together and compared to known functions of RboP/GlcNAc WTA type our data suggesting a similar role of this unique L-type WTA.

T728

439303-439422

Epistemic_statement

denotes

However, there has been a controversy regarding the mechanism of phagosomal escape, which is only partially understood.

T729

440802-440978

Epistemic_statement

denotes

Discussion: Our data suggest that PSM , but not PSM , -toxin, or PVL, are required for phagosomal escape of the staphylococcal strains 6850, LAC, and MW2 in 293 and HeLa cells.

T730

440979-441041

Epistemic_statement

denotes

Surprisingly, -toxin appears not to be required in this model.

T731

441296-441459

Epistemic_statement

denotes

Results: Binding of complement regulators CFHR1, CFHR2, and CFHR5 to immobilized CRASP-4 could be detected by Western blotting and ELISA using specific antibodies.

T732

441563-441672

Epistemic_statement

denotes

However, binding of serum-purified CFH to recombinant CRASP-4 was demonstrated by ELISA and Far Western blot.

T733

442231-442337

Epistemic_statement

denotes

Seemingly, binding of different CFHRs is not sufficient to protect cells from complement-mediated killing.

T734

442338-442466

Epistemic_statement

denotes

Thus, our data strongly suggest that CRASP-4 plays a subordinate but supporting role in complement resistance of B. burgdorferi.

T735

443783-444090

Epistemic_statement

denotes

Two "clustered regularly interspaced short palindromic repeats" (CRISPRs) were identified having up to 19 spacers, some with homologies to S. pyogenes phages; this may explain the lack of complete phages in the AC-2713 genome and the low degree of rearrangements in SDSE genomes, in contrast to S. pyogenes.

T736

444581-444862

Epistemic_statement

denotes

Comparative analyses revealed a high degree of homology and colinearity with the published S. dysgalactiae genomes and closer relationships to S. pyogenes (based on available genomes) than to other beta-hemolytic streptococci including groups C and G streptococci of animal origin.

T737

444863-445122

Epistemic_statement

denotes

Conclusion/Discussion: AC-2713, an SDSE possessing Lancefield's group A antigen, is highly homologous to other S. dysgalactiae and more closely related to S. pyogenes than to other streptococcal species, including groups C and G streptococci of animal origin.

T738

445390-445544

Epistemic_statement

denotes

The versatile interplay between pathogenic bacteria and its host depend on numerous interactions of bacterial surface structures and host matrix proteins.

T739

446446-446540

Epistemic_statement

denotes

Nevertheless, the receptor on the bacterial side as well as on the host side is still unknown.

T740

446820-447051

Epistemic_statement

denotes

Surface plasmon resonance (SPR) studies with TSP-1 immobilized on CM5 biosensors and ligand overlay assays revealed a potential proteinous binding partner on the bacterial side in Staphylococcus aureus and Streptococcus pneumoniae.

T741

447217-447304

Epistemic_statement

denotes

The results indicated binding candidates whose specific binding is under investigation.

T742

447305-447575

Epistemic_statement

denotes

The interaction of TSP-1 with different Gram-positive bacteria via surface exposed proteins is most likely important during colonization and bacterial dissemination and could be beneficial in the development of severe infections like infective endocarditis or pneumonia.

T743

447861-448082

Epistemic_statement

denotes

Lantibiotics (lanthionine containing antibiotics) are ribosomally produced bacterial peptide antibiotics that show interesting antibacterial activities even in the nanomolar range against (multiresistant) human pathogens.

T744

448235-448451

Epistemic_statement

denotes

These rare amino acids form intramolecular rings that are essential for the three-dimensional structure of lantibiotics, their enhanced stability against proteases and oxidation and convey the antimicrobial activity.

T745

448452-448619

Epistemic_statement

denotes

These features make lantibiotics interesting candidates or lead structures for novel antimicrobial applications in medical and food industry (Ross and Vanderas, 2011).

T746

450482-450665

Epistemic_statement

denotes

Despite that, much less is known in detail about how bacteria control the interplay between degradation and new synthesis of peptidoglycan to coordinate cell division and cell growth.

T747

450666-450892

Epistemic_statement

denotes

Two-component regulatory systems (TCSs), composed of a sensor histidine-kinase and a cognate response regulator protein, play a predominant role in the way how bacteria respond and adapt to environmental and stress conditions.

T748

452085-452393

Epistemic_statement

denotes

Interestingly, even heparin-naïve patients can generate IgG-antibodies specific for PF4/heparin complexes as soon as 4 days after exposure to heparin, presumably because these patients have encountered complexes similar to PF4/heparin before such as PF4 bound to anionic bacterial surfaces during infections.

T749

452394-452541

Epistemic_statement

denotes

Likely candidates for negatively charged molecules on bacterial surfaces are lipopolysaccharides (LPS) and teichoic acids (TA) as well as proteins.

T750

452892-453024

Epistemic_statement

denotes

Surprisingly, E. coli and S. typhimurium mutants with successively shortened LPS-backbone displayed increasing PF4 binding capacity.

T751

453149-453323

Epistemic_statement

denotes

However, the E. coli mutant waaA is additionally deficient in the 3deoxy-D-manno-octulosonic acids (KDO) suggesting that Lipid A is the structure contributing to PF4-binding.

T752

453805-454058

Epistemic_statement

denotes

Thus, by acting as a bacteria-opsonizing protein, PF4 is able to induce a humoral immune response specific for a wide variety of bacterial species and might therefore be an ancient host defense mechanism at the interface of innate and adaptive immunity.

T753

454059-454209

Epistemic_statement

denotes

HIF-1 is the key transcriptional factor involved in the adaption process of mammals to hypoxia and plays a crucial role in, e.g., cancer angiogenesis.

T754

454210-454299

Epistemic_statement

denotes

Recent evidence suggests a leading role of HIF-1 in inflammatory and infectious diseases.

T755

455031-455297

Epistemic_statement

denotes

One of the upregulated genes was lysyl oxidase, (lox), a copper-dependent amine oxidase, which catalyzes the cross linking of collagen and elastin molecules in the extracellular matrix and might be involved in the development of a fibrosis after S. aureus infection.

T756

455558-455710

Epistemic_statement

denotes

The role of lox in abscess formation and, moreover, in chronic infections known to result in fibrous scarring of tissues needs to be further elucidated.

T757

456059-456153

Epistemic_statement

denotes

Q-fever is a mild flu-like illness, but can be associated with chronic or even fatal outcomes.

T758

456240-456422

Epistemic_statement

denotes

For intracellular pathogens such as C. burnetii, manipulation of host cell pathways is important to ensure a productive infection and may play a role in establishing chronic disease.

T759

456534-456671

Epistemic_statement

denotes

One of these substrate proteins, AnkG, inhibits pathogeninduced apoptosis, probably through binding to the host cell protein p32 (gC1qR).

T760

456672-456779

Epistemic_statement

denotes

The mitochondrial matrix protein p32 seems to be a pro-apoptotic protein, however the mechanism is unknown.

T761

457111-457235

Epistemic_statement

denotes

The p32 protein seems to be involved in bridging a signaling pathway that extends from the mitochondria to the cell nucleus.

T762

457236-457348

Epistemic_statement

denotes

Here, we aim to investigate how the interaction of AnkG with p32 determines the anti-apoptotic activity of AnkG.

T763

457349-457433

Epistemic_statement

denotes

Therefore, we tested whether the interaction of AnkG with p32 is direct or indirect.

T764

457512-457699

Epistemic_statement

denotes

As p32 is a mitochondrial protein we hypothesized that if the anti-apoptotic activity of AnkG is mediated by p32, AnkG only inhibits the intrinsic and not the extrinsic apoptosis pathway.

T765

457700-457767

Epistemic_statement

denotes

This hypothesis was confirmed using ectopic expression experiments.

T766

457896-458010

Epistemic_statement

denotes

Interestingly, ectopic expression showed that the N-terminus (AnkG1-69) is nuclear, while AnkG70-339 is cytosolic.

T767

458084-458246

Epistemic_statement

denotes

These data suggest that nuclear localisation as well as binding to p32 is necessary for the antiapoptotic activity of the Coxiella burnetii effector protein AnkG.

T768

458613-458704

Epistemic_statement

denotes

It is shown that DsdA enables S. saprophyticus to cleave Dserine into pyruvate and ammonia.

T769

458705-458778

Epistemic_statement

denotes

This is probably a factor that enables colonization of the urinary tract.

T770

459791-459906

Epistemic_statement

denotes

To take account of this results SSP1070 appears to be the major player in D-serine uptake in S. saprophyticus 7108.

T771

459907-460051

Epistemic_statement

denotes

The knowledge of D-serine transport and metabolism will presumably offer us more insights in to the physiology of virulence of S. saprophyticus.

T772

460600-460825

Epistemic_statement

denotes

After synthesis in the cytosol and Sec-mediated transport across the inner membrane into the periplasm, the translocator domain forms a beta-barrel pore in the outer membrane, presumably with the help of the Bam complex (2) .

T773

461402-461601

Epistemic_statement

denotes

Whereas the surface-localized parts of the protein are functionally well described, the topology and insertion of the N-terminal membrane domain and the translocation process have not been described.

T774

461789-461930

Epistemic_statement

denotes

Herefrom we got a prediction of the signal peptide and twelve different -strands, which might build up the -barrel within the outer membrane.

T775

462216-462438

Epistemic_statement

denotes

Moreover, we came to believe that Intimin (Int) and Invasin (Inv), two major pathogenicity factors of E.coli and Yersinia, are monomeric autotransporters, with the remarkable difference that their domain order is reversed.

T776

462552-462693

Epistemic_statement

denotes

It has clinical significance in abscess formation and has recently been suggested to play a pathogenic role in patients with cystic fibrosis.

T777

462827-462980

Epistemic_statement

denotes

While a considerable percentage of S. anginosus strains display a prominent ß-haemolytic phenotype, the corresponding genes have not been identified yet.

T778

462981-463107

Epistemic_statement

denotes

In different streptococcal species the ß-haemolysin is a modified short peptide (SLS) that is related to Class I bacteriocins.

T779

463420-463591

Epistemic_statement

denotes

This library was screened for mutants showing a loss of the ß-haemolytic phenotype on blood agar plates and non-haemolytic mutants were selected for further investigation.

T780

463914-463994

Epistemic_statement

denotes

ORFs corresponding to all of the 9 sag genes (sagA to sagI) could be identified.

T781

464299-464510

Epistemic_statement

denotes

Haemolytic activity was only observed with whole cells, but not in the supernatant, indicating that like SLS of S. pyogenes, the S. anginosus haemolysin is able to lyse erythrocytes only in cell-associated form.

T782

464706-464975

Epistemic_statement

denotes

A magnetic isolation method to analyze differential Chlamydia pneumoniae interacting protein profiles in persistence infection Introduction: Chlamydia pneumoniae (Cpn) is an obligate intracellular bacterial pathogen and causes acute infections of the respiratory tract.

T783

464976-465238

Epistemic_statement

denotes

Further, Cpn can also cause prolonged or chronic infections which may be due to persistent infections in respiratory and non-respiratory tissues and have been implicated in the development of a number of chronic diseases such as asthma, COPD and atherosclerosis.

T784

465358-465464

Epistemic_statement

denotes

However, host-pathogen interacting proteins during persistent infection have not been investigated so far.

T785

467205-467389

Epistemic_statement

denotes

Conclusion/Discussion: Our results indicate the suitability of the novel magnetic isolation method to identify pathogen-host interacting proteins in a targeted and untargeted approach.

T786

467772-467885

Epistemic_statement

denotes

The reason why ABU-associated E. coli strains do not evoke symptoms in the host is not completely understood yet.

T787

467886-468012

Epistemic_statement

denotes

Many ABU E. coli isolates seem to lack virulence associated phenotypes, although they carry many typical UPEC virulence genes.

T788

468013-468187

Epistemic_statement

denotes

It has been shown that such isolates express less virulence factors and that there is an evolution towards commensalism because of virulence attenuation and genome reduction.

T789

468188-468448

Epistemic_statement

denotes

Alterations in essential virulence genes including single base mutations, deletions or DNA rearrangements might be a general mechanism for long-term colonizing mucosal pathogens to evolve towards commensalism, consistent with a low immune response of the host.

T790

468449-468570

Epistemic_statement

denotes

In this study, the importance of the two-component system (TCS) BarA/UvrY for urovirulence of E. coli should be analysed.

T791

469075-469235

Epistemic_statement

denotes

This may indicate that uvrY is (i) a mutation hot spot and (ii) under positive selection during bacterial adaption during long-term growth in the urinary tract.

T792

469236-469476

Epistemic_statement

denotes

To correlate uvrY nucleotide sequence variability with prolonged colonization of the urinary tract, the uvrY gene was sequenced in 216 E. coli strains representing ABU and acute UTI isolates as well as a control group of commensal variants.

T793

469714-469923

Epistemic_statement

denotes

Despite being key for Staphylococcus epidermidis pathogenicity in implantassociated infections, large proportions of invasive Staphylococcus epidermidis isolates do not form biofilms under in vitro conditions.

T794

469924-470092

Epistemic_statement

denotes

We here tested the hypothesis that this apparent paradox is related to the existence of superimposed regulatory systems suppressing a multi-cellular biofilm life style.

T795

470814-471107

Epistemic_statement

denotes

Hence, our results provide first evidence that key regulator sarA, while promoting polysaccharide intercellular adhesin dependent biofilm formation on one hand, negatively controls S. epidermidis biofilm formation by suppressing Embp production and autolysis-related eDNA release on the other.

T796

472770-472933

Epistemic_statement

denotes

Although the interaction of pneumococci with vitronectin and its cellular consequences were demonstrated, the pneumococcal adhesin for vitronectin remains unknown.

T797

473991-474148

Epistemic_statement

denotes

In conclusion, PspC possesses vitronectin-binding activity, however, its role in pneumococcal pathogenesis via vitronectin has to be assessed in more detail.

T798

474168-474429

Epistemic_statement

denotes

Gerlach 1 1 Robert Koch-Institut, NG3, Wernigerode, Deutschland Salmonella enterica serovar Typhimurium (S. Typhimurium) is a facultative intracellular pathogen able to cause acute gastroenteritis and diarrhea in humans and a typhoid fever-like disease in mice.

T799

474783-474899

Epistemic_statement

denotes

SiiA and SiiB are two additional SPI-4-encoded inner membrane-associated proteins that might regulate SiiE function.

T800

474900-474983

Epistemic_statement

denotes

However, expression of SPI-4 is controlled by regulators encoded outside the locus.

T801

476626-476826

Epistemic_statement

denotes

We could immunodetect distinct sets of protein complexes for C-terminal HBH-tagged SiiB and SirA using an antibody against the RGS-H6 peptide implying low cross-reactivity against non-tagged proteins.

T802

476827-476993

Epistemic_statement

denotes

For MS analyses, we included two negative controls to eliminate the possibility of identifying background and non-specifically bound proteins as interacting partners.

T803

476994-477128

Epistemic_statement

denotes

Our results will provide new insights into the function of SPI-4 for successful adhesion to and subsequent colonization of host cells.

T804

477129-477225

Epistemic_statement

denotes

Y. Novotny* 1 , L. Marlinghaus 1 , M. Korte 1 , S. Neumann 1 , S. Gatermann 1 , F. Szabados 1 1

T805

477226-477453

Epistemic_statement

denotes

Staphylococcus lugdunensis is a coagulase-negative staphylococcus (CNS) that can cause severe infections, like skin and soft tissue infections, sepsis and potentially fatal endocarditis, similar to diseases caused by S. aureus.

T806

478445-478550

Epistemic_statement

denotes

This indicates that the SLUSH gene cluster was absent or the gene cluster was different in these strains.

T807

478767-479006

Epistemic_statement

denotes

The high occurrence of the hemolysin genes also indicate that the hemolysis attribute is less likely determined by a single hemolysin gene but rather a supposed combined effect of several hemolysin genes or differences in their expression.

T808

479169-479367

Epistemic_statement

denotes

We hypothesize that initial binding of FnBPs to apically located receptors increases the permeability of the endothelial barrier and thus facilitates access to the basolateral pool of 5 1 integrins.

T809

481043-481220

Epistemic_statement

denotes

Partial protection by genistein and PP2 suggests that Src family kinases mediate an increased permeability of endothelial cells, supposedly by affecting tight junction proteins.

T810

481221-481318

Epistemic_statement

denotes

This effect might be mediated by phosphorylation of either tight junction or regulatory proteins.

T811

481319-481534

Epistemic_statement

denotes

Further studies will include scanning electron microscopy to determine changes in cell morphology, immunodetection and localization of tight junction proteins and siRNA transfection to knock down Src family kinases.

T812

481701-481842

Epistemic_statement

denotes

They are thought to be implicated in colonization, bacterial adhesion to and invasion into host cells, and immune evasion mechanisms as well.

T813

483139-483269

Epistemic_statement

denotes

Only a few lipoproteins are less abundant, however, the corresponding exoproteome of the lsp mutant showed no significant changes.

T814

483600-483712

Epistemic_statement

denotes

During delivery it can be transmitted from the mother to the newborn and cause sepsis, pneumonia and meningitis.

T815

483821-483993

Epistemic_statement

denotes

The laminin receptor on brain endothelial cells has recently been shown to be crucial for the initiation of contact between meningeal pathogens and the blood brain barrier.

T816

484656-484830

Epistemic_statement

denotes

A highly disordered loop spanning residues 123-138 has been observed and it has been shown to play a role in metal uptake and release of the protein in homologous structures.

T817

485385-485660

Epistemic_statement

denotes

Being ubiquitous in all the serotypes of Group B Streptococcus (GBS), a detailed knowledge of the amino acid residues critical for laminin binding may allow the future development of targeted antimicrobial strategies interfering with the adhesion properties of S. agalactiae.

T818

485954-486152

Epistemic_statement

denotes

Persistent infection is suggested to promote disease progression in chronic obstructive pulmonary disease (COPD) in which epithelial to mesenchymal cell transition (EMT) is known to be a key factor.

T819

487386-487476

Epistemic_statement

denotes

Interestingly, Cpn could be rescued from IFN-induced persistence under hypoxic conditions.

T820

487969-488070

Epistemic_statement

denotes

Acute and persistent Cpn induce EMT in lung cells that is even more pronounced when oxygen is scarce.

T821

488468-488610

Epistemic_statement

denotes

In Staphylococcus aureus, CcpA has been shown to modulate the expression of metabolic genes and virulence determinants in response to glucose.

T822

489438-489699

Epistemic_statement

denotes

However, transcription of hla (encoding a-hemolysin), and of RNAIII, the effector molecule of the agr locus, were significantly increased by the mutation, suggesting that NWMN_0641 acts as a repressor of hla and RNAIII, and as an activator of cap transcription.

T823

490321-490463

Epistemic_statement

denotes

In S. aureus, ClpB and ClpC are both regulated by the repressor CtsR, with ClpC probably supporting the active conformation of this repressor.

T824

490694-490822

Epistemic_statement

denotes

ClpB, and to a lesser extent, ClpC have been shown to promote the intracellular multiplication of S. aureus in epithelial cells.

T825

491770-491970

Epistemic_statement

denotes

In terms of invasiveness, however, the clpB and clpBC mutants possessed significantly decreased internalization capacities, probably due to lowered productions of fibronectin binding proteins A and B.

T826

491971-492312

Epistemic_statement

denotes

These findings suggest that ClpB contributes to the invasiveness of this pathogen, but does not influence the persistence capacity of this organism, while a functional ClpC seems to decrease the intracellular survival capacity of S. aureus but does not affect the invasiveness of this organism, irrespective of its impact on clpB expression.

T827

492313-492485

Epistemic_statement

denotes

Aggregatibacter actinomycetemcomitans is a Gram-negative commensal bacterium of the oral cavity which has been associated with the pathogenesis of aggressive periodontitis.

T828

492486-492622

Epistemic_statement

denotes

However, genetic mechanisms underlying host susceptibility to periodontal infection and to periodontitis progress are still ill-defined.

T829

493914-494178

Epistemic_statement

denotes

Our results indicate that NADPH oxidase is important for resistance of the murine oral cavity against A. actinomycetemcomitans colonization which is clearly associated with alveolar bone destruction and influx of inflammatory cells in NADPH oxidase-deficient mice.

T830

494179-494327

Epistemic_statement

denotes

This model should give further insights into the molecular and genetic mechanisms of the A. actinomycetemcomitans induced periodontitis development.

T831

495464-495619

Epistemic_statement

denotes

These data show that all tested Y. enterocolitica and Y. pseudotuberculosis YadA variants are capable to mediate comparable MV in Y. enterocolitica WA-314.

T832

496189-496323

Epistemic_statement

denotes

Media, however, used for culture of Mycobacterium (M.) tuberculosis are quite complex and contain several carbon and nitrogen sources.

T833

496324-496551

Epistemic_statement

denotes

Here we show that M. tuberculosis growing in minimal medium with glucose as carbon source also metabolizes other supplemented ingredients like the fatty acids contamination of albumine and surprisingly also the detergent tween.

T834

496920-497057

Epistemic_statement

denotes

Results: Using minimal medium with fully 13 C-labelled glucose, we expected to measure 1 % at the most non labelled amino acids by GC-MS.

T835

497058-497122

Epistemic_statement

denotes

However it turned out that 20 % of metabolites are not labelled.

T836

497277-497586

Epistemic_statement

denotes

Improvement of the washing steps did not change the fraction of non labelled amino acids, however the substitution of albumine (contaminated with 1 % fatty acids) against highly purified albumine (contaminated with 0.02 % fatty acids) could decrease the fraction of non labelled amino acids to less than 10 %.

T837

497587-497693

Epistemic_statement

denotes

When we replaced tween with tyloxapol we could further diminish the non labelled amino acids to about 5 %.

T838

497694-497929

Epistemic_statement

denotes

Further improvement of the protocol for preparation of M. tuberculosis cell extracts by using cellulose nitrate filter instead of harvesting the cells by centrifugation could diminish the part of non labelled amino acids to almost 0 %.

T839

498546-498718

Epistemic_statement

denotes

Identification and characterization of these interactions is one challenging task of the post-genomic era and crucial for understanding of the molecular bases of virulence.

T840

500518-500681

Epistemic_statement

denotes

Typhimurium (S. Typhimurium), luminescence measurements revealed significant higher signal with full length SipA compared to its truncated version lacking the CBD.

T841

501305-501446

Epistemic_statement

denotes

Mutations of the cov gene have been associated with increased hemolytic activity, but impaired intracellular survival of GBS in granulocytes.

T842

502213-502365

Epistemic_statement

denotes

Interestingly, the nonhemolytic mutants were able to survive in the intracellular environment in significantly higher numbers than the hemolytic strain.

T843

502447-502725

Epistemic_statement

denotes

To exclude the possibility that the observed differences in survival were due to host cell death induced by the hemolytic but not the non-hemolytic strain, Lactate Dehydrogenase (LDH) assays were carried out and confirmed the better survival capacity of the nonhemolytic strain.

T844

502726-502822

Epistemic_statement

denotes

The ß-hemolysin of GBS has previously been described as a potent inducer of IL-8 in macrophages.

T845

502922-503105

Epistemic_statement

denotes

While a considerable release of IL-8 could be observed, however we could not find a significant difference in the ability of hemolytic or nonhemolytic strains to induce the chemokine.

T846

503338-503612

Epistemic_statement

denotes

In conclusion, our results indicate that the S. agalactiae ßhemolysin has a strong influence on the intracellular survival of GBS and that a tightly controlled regulation of ß-hemolysin expression is required for the successful establishment of GBS in different host niches.

T847

503613-503773

Epistemic_statement

denotes

In conclusion, the ability to express ZnuD upon zinc starvation was well conserved among meningococci, which argues for an essential role of meningococcal ZnuD.

T848

503774-503880

Epistemic_statement

denotes

It is intriguing that inactivating ZnuD mutation events seem to be restricted to only two clonal lineages.

T849

504014-504155

Epistemic_statement

denotes

In our work, we firstly describe that 1-L-MT, but not 1-D-MT, can act as a nutritive substrate that replaces tryptophan in in vitro cultures.

T850

504498-504651

Epistemic_statement

denotes

A detailed analysis showed that 1-L-MT, in contrast to 1-D-MT, is incorporated in human T-cell proteins when tryptophan is lacking in the culture medium.

T851

504652-504891

Epistemic_statement

denotes

In summary our data indicate that 1-L-MT inhibits the IDO-mediated antiproliferative activities via two independent effects: On the one hand 1-L-MT acts as a competitive enzyme inhibitor and therefore reduces tryptophan degradation by IDO.

T852

504892-505027

Epistemic_statement

denotes

On the other hand 1-L-MT can replace tryptophan in protein biosynthesis and therefore allows bacterial, parasitical or cellular growth.

T853

505182-505578

Epistemic_statement

denotes

The hypothetical type VI secretion protein BPSS1504 is involved in virulence of Burkholderia pseudomallei Background: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strains, especially the Panton-Valentine-leukocidin (PVL) producing strain USA300, have been associated with severe necrotizing infections, such as necrotizing pneumonia, which have high mortality rates.

T854

506932-507180

Epistemic_statement

denotes

However, when we treated the epithelial cell monolayer with supernatants of human granulocytes, which were lysed by PVL and PR8, we found a dosedependent destruction of the epithelial cell monolayer, mainly caused by detachment of epithelial cells.

T855

507448-507610

Epistemic_statement

denotes

The influenza virus has an activating impact on epithelial cells that could result in massive recruitment of granulocytes, which can be subsequently lysed by PVL.

T856

507840-507992

Epistemic_statement

denotes

These results from our cell culture models suggest that PVL and influenza virus can act together and are possible agents to cause necrotizing pneumonia.

T857

508763-508945

Epistemic_statement

denotes

The collaborative work between the Dandekar and Hensel groups should lead to a comprehensive understanding of the metabolic requirements of the intracellular lifestyle of Salmonella.

T858

509320-509597

Epistemic_statement

denotes

Towards an integrated model and profiting from SPP1316, we will do comparisons of the Salmonella lifestyle with other pathogens and their metabolic requirements during infection such as cytoplasmic lifestyle found in Listeria or within a membrane compartment as for Legionella.

T859

510031-510117

Epistemic_statement

denotes

Interestingly, it is also present in other uropathogenic bacteria like E. coli (UPEC).

T860

510272-510384

Epistemic_statement

denotes

Therefore the uncommon ability to degrade D-serine may play an important role for the virulence of uropathogens.

T861

510385-510498

Epistemic_statement

denotes

In addition, the presence of D-serine may be used as a cue by uropathogens for the presence in the urinary tract.

T862

511305-511501

Epistemic_statement

denotes

These results lead us to the hypothesis that D-serine indeed is used as a cue for the presence within the urinary tract and regulates pathways that are important for viability in this environment.

T863

512317-512417

Epistemic_statement

denotes

Previous experiments have indicated that a SdrI mutant showed decreased fibronectin binding in vivo.

T864

513249-513343

Epistemic_statement

denotes

Suprisingly, the UafA knock out mutant was also associated with decreased fibronectin binding.

T865

513622-513872

Epistemic_statement

denotes

Staphylococcus aureus, the cause of a wide spectrum of severe communityacquired and nosocomial infections, is recently acknowledged as an intracellular pathogen, as it can be internalized and persist in nonprofessional phagocytic cells in vitro [1] .

T866

514248-514448

Epistemic_statement

denotes

The aim of this study is to comparatively investigate the adaptive response of S. aureus RN1GH wild type and isogenic agr mutant cells upon co-internalization by human bronchial epithelial cells (S9).

T867

514449-514614

Epistemic_statement

denotes

The accessory gene regulator (agr) is one of the major global regulators of S. aureus virulence, which positively influences the synthesis ofhemolysin and proteases.

T868

515078-515246

Epistemic_statement

denotes

The striking advantage of a co-infection assay would be that both strains are being internalized simultaneously and adapt to the host under exactly the same conditions.

T869

515379-515572

Epistemic_statement

denotes

(C. trachomatis) are the most frequent transmitted sexually disease in women that may result in severe clinical sequelae like pelvic inflammatory disease (PID), tubal occlusion and infertility.

T870

515573-515791

Epistemic_statement

denotes

It is suggested that once the acute infection is not efficiently cleared by the immune system intracellular persistence of chlamydiae eventually occur, leading to chronic inflammatory processes within infected tissues.

T871

515792-515969

Epistemic_statement

denotes

We could recently show that IFN-induced persistence of C. trachomatis in human fallopian tube cells can be overcome by decreasing the environmental oxygen concentration (<3%O2).

T872

516080-516259

Epistemic_statement

denotes

The aim of our study was to characterize hypoxia induced reactivation of intracellular chlamydial growth with respect to pro-inflammatory immune responses and MAPkinase signaling.

T873

516811-516930

Epistemic_statement

denotes

Preliminary experiments suggest that ERK1/2 and p38 MAPkinases are activated under normoxic but not hypoxic conditions.

T874

517301-517454

Epistemic_statement

denotes

Intracellular reactivation of formerly persistent chlamydiae might perpetuate inflammatory processes that result in chronic sequelea in diseased tissues.

T875

518902-519092

Epistemic_statement

denotes

Interestingly, mutation of the Walker A motif as well as deletion of the entire ATPase domain lead to a twofold enhanced binding to sulfated ECM structures, like heparin and dextran sulfate.

T876

519393-519670

Epistemic_statement

denotes

The findings that the ecto-ATPase activity of OppA is essential for cytoadhesion of M. hominis whereas the CS1 region is more involved in ECM-binding suggest that these two functional regions play a different role in patho-physiological processes of host-pathogen interactions.

T877

520144-520459

Epistemic_statement

denotes

In spite of variations in phage type, PFGE and resistance pattern within the emerging monophasic strains one type characterised by phage type DT193, PFGE pattern STYMXB.0131 and tetra-drugresistance towards antibiotics including ampicillin, streptomycin, sulfamerazine and tetracycline clearly dominates in Germany.

T878

520460-520550

Epistemic_statement

denotes

Meanwhile the same kind of strains is of increasing concern in various European countries.

T879

520906-520946

Epistemic_statement

denotes

Transcripts have been shown for 24 ORFs.

T880

521074-521190

Epistemic_statement

denotes

Protein BLAST analyses revealed several phage-related genes, indicating that the insertion might be of phage-origin.

T881

521246-521325

Epistemic_statement

denotes

Our experiments suggest that its product is secreted but probably not via T3SS.

T882

521454-521598

Epistemic_statement

denotes

Further, it had been shown that the island is able to form a circular intermediate and therefore seems to be mobilised under certain conditions.

T883

523088-523230

Epistemic_statement

denotes

However, the latter acquired putative virulence and fitness associated factors, which may substitute the classical yersinial virulence traits.

T884

523690-523763

Epistemic_statement

denotes

However, it has suffered successive deletions in strains Y8265 and Y5307.

T885

524098-524180

Epistemic_statement

denotes

The island has a functional integrase and can leave its tRNA-Asn integration site.

T886

524314-524486

Epistemic_statement

denotes

The acquired putative virulence and fitness-associated determinants may play an important role in host pathoadaptation and support dissemination of this group of pathogens.

T887

524487-524657

Epistemic_statement

denotes

Staphylococcus aureus adherence to host structures, which is a critical first step in S. aureus pathogenesis, is mediated by multiple adhesins with overlapping functions.

T888

524658-524981

Epistemic_statement

denotes

The role of some adhesins, particularly the MSCRAMs (microbial surface component recognizing adhesive matrix molecule) is already well established, whereas the function of the secreted and rebinding SERAMs (secretable expanded repertoire adhesive molecule), such as Emp (extracellular matrix binding protein) is less clear.

T889

525502-525604

Epistemic_statement

denotes

The C-terminus of the Emp protein (Emp2, Emp3) appears to be responsible for the binding to S. aureus.

T890

525927-526055

Epistemic_statement

denotes

This could also be confirmed by Emp binding assays to different eukaryotic cell types, such as endothelial and epithelial cells.

T891

526263-526392

Epistemic_statement

denotes

However, Emp binding could not be broken down to short amino acid sequences, in fact, binding is mediated by the whole fragments.

T892

526590-526685

Epistemic_statement

denotes

We hypothesize, that the contact to the binding partner is essential for the protein structure.

T893

526686-526891

Epistemic_statement

denotes

Taken together, our results indicate that the N-terminal part of Emp mediates the binding to host structures, whereas the C-terminal part of Emp is responsible for the rebinding to the bacterial cell wall.

T894

528401-528573

Epistemic_statement

denotes

Ongoing studies are aimed to identify the gene expression profiles of S. aureus strains persistent over a period of several years in the presence of P. aeruginosa isolates.

T895

529280-529441

Epistemic_statement

denotes

Although SIFs were identified long back, their role in the intracellular life of Salmonella and the molecular mechanism underlying the dynamics is not yet known.

T896

529442-529593

Epistemic_statement

denotes

However, work by others and our group has identified that SIFs lie next to the microtubule tracks and are often associated or linked to motor proteins.

T897

529594-529756

Epistemic_statement

denotes

Because of these observations we hypothesized that the SIFs move along the microtubule tracks and require the activities of the motor proteins kinesin and dynein.

T898

529939-530030

Epistemic_statement

denotes

However, these approaches render the cells compromised even before the bacterial infection.

T899

530719-530787

Epistemic_statement

denotes

gallolyticus (Sgg) (former S. bovis biotype I) as a causative agent.

T900

530788-530899

Epistemic_statement

denotes

Furthermore, the knowledge of virulence factors that contribute to the pathogenesis in Sgg IE is still limited.

T901

533033-533275

Epistemic_statement

denotes

The alignment of microarray data and already evaluated phenotypic data, including ECM-binding, adhesion and invasion to host cells and biofilm formation capability of 41 strains, will substantiate the underlying genomic based pathomechanisms.

T902

534835-535079

Epistemic_statement

denotes

Interestingly, using far western experiments we identified an interaction of Pmp21 with itself as with all other Pmps tested possibly suggesting that homo-and/or heteromeric Pmp adhesion complexes might be formed on the chlamydial cell surface.

T903

535398-535646

Epistemic_statement

denotes

Cell fractionation experiments revealed that cleaved Pmp-fragments are partially released from the chlamydial surface and may exist in the inclusion lumen and possibly in the host cytosol perhaps serving an additional function as effector proteins.

T904

535647-535936

Epistemic_statement

denotes

Most interestingly, using immunofluorescence microscopy we detected that individual Pmp proteins were expressed only in a fraction of the inclusions analyzed possibly indicating a form of antigenic variation similar to what recently has been described for Pmp proteins from C. trachomatis.

T905

536051-536202

Epistemic_statement

denotes

The human pathogen Chlamydia pneumoniae nucleates and stabilizes F-actin via the secreted Cpn0572 protein to support host cell entry R. Zrieq* 1 , J.H.

T906

536467-536642

Epistemic_statement

denotes

Like other pathogenic bacteria, It is believed that Chlamydiae deliver effector proteins to recruit F-actin at the site of entry to trigger their own entry into the host cell.

T907

537059-537164

Epistemic_statement

denotes

About 20 minutes after infection Cpn0572 is secreted and could be found associated with the host F-actin.

T908

537827-537995

Epistemic_statement

denotes

Indeed, we could show that in yeast Cpn0572 stabilizes F-actin against the actin destabilizing drug Latrunculin A implying that Cpn0572 inhibits actin depolymerization.

T909

538150-538333

Epistemic_statement

denotes

These results were extended to in vitro experiments using mammalian F-actin and cofilin proteins, in which we could show that presence of Cpn0572 abrogates cofilin binding to F-actin.

T910

538334-538563

Epistemic_statement

denotes

In line with these data the actin clumps in Cpn0572 transfected HEK-293 cells were resistant to the actin depolymerizing drug cytochalasin D suggesting that Cpn0572 is indeed able to inhibit actin depolymerization in human cells.

T911

538700-538828

Epistemic_statement

denotes

Finally, a deletion analysis identified a central domain within Cpn0572 (DUF1547) which is crucial for interaction with F-actin.

T912

539578-539688

Epistemic_statement

denotes

During the first step of infection the intracellular pathogen Listeria monocytogenes is located in phagosomes.

T913

539863-540114

Epistemic_statement

denotes

L. monocytogenes is equipped with a peptide sensing system which is homologous to the Staphylococcus aureus agr system and has been shown to be involved in the regulation of biofilm formation, in vitro and in vivo virulence and global gene expression.

T914

540980-541084

Epistemic_statement

denotes

This strongly suggests that the agr system of L. monocytogenes is subject to an auto-regulatory circuit.

T915

541523-541758

Epistemic_statement

denotes

Interestingly, a putative AgrA-binding motif was identifies in promoter of -prfA, the major virulence regulator of L. monocytogenes which could explain the strong regulation of this gene in the agrD-deletion mutant observed previously.

T916

542242-542334

Epistemic_statement

denotes

ADEPs act via a yet unprecedented mechanism by dysregulating the caseinolytic protease ClpP.

T917

542691-542867

Epistemic_statement

denotes

Although the activity of ADEPs can be explained on the molecular level of its target ClpP, the specific events that finally lead to bacterial cell death still remained unknown.

T918

544805-544905

Epistemic_statement

denotes

However, MRSA strains with reduced susceptibility to vancomycin have emerged during the last decade.

T919

544906-545024

Epistemic_statement

denotes

Due to increased antibiotic treatment failure, there is an obvious need to understand how bacteria develop resistance.

T920

545414-545700

Epistemic_statement

denotes

In the current study, antimicrobial susceptibility testing of strain VC40 additionally revealed cross resistance against the lipopeptide antibiotic daptomycin, which has recently been introduced for the treatment of complicated skin and skin structure infections (cSSSI) caused by MRSA.

T921

546314-546489

Epistemic_statement

denotes

Here, strain VC40 was characterized by an abnormal cell envelope morphology including an increased cell wall thickness that may result from deregulated VraRS or WalKR systems.

T922

546490-546630

Epistemic_statement

denotes

Cell wall thickening has previously been linked to vancomycin resistance and even has been correlated with daptomycin cross resistance (4) .

T923

546631-546727

Epistemic_statement

denotes

However, these findings alone cannot explain the high-level resistance phenotype of strain VC40.

T924

546728-546960

Epistemic_statement

denotes

Further characterization of strain VC40 is necessary and will provide important information on how the accumulation of mutations resulted in the autonomous development of vancomycin and daptomycin high-level resistance in S. aureus.

T925

547189-547339

Epistemic_statement

denotes

In vivo, the bacteria very likely face adverse replication conditions, in particular when the immune response is activated and cytokines are secreted.

T926

547340-547466

Epistemic_statement

denotes

Such conditions can be mimicked in a number of ways, for instance by the addition of -lactam antibiotics to cultures in vitro.

T927

547536-547839

Epistemic_statement

denotes

The persistent phenotype is characterized by enlarged, aberrant reticulate bodies (RBs; the replicative form of Chlamydia), which are neither able to divide nor to re-differentiate into infectious elementary bodies (EBs) but which can be re-activated upon withdrawal of the persistence-inducing reagent.

T928

547840-548059

Epistemic_statement

denotes

As persistent infections are thought to be relevant for the outcome of chlamydial disease, especially in chronic infections, we are investigating the development of the chlamydial inclusion during this persistent state.

T929

548314-548410

Epistemic_statement

denotes

Although there were only few of these RBs per inclusion, the vacuole grew substantially in size.

T930

548411-548532

Epistemic_statement

denotes

We have proposed that growth of the inclusion during productive infection requires the secreted chlamydial protease CPAF.

T931

548932-549185

Epistemic_statement

denotes

These results suggest that even upon entry into the 'persistent' state during treatment with penicillin G, C. trachomatis can maintain the machinery for lipid acquisition and inclusion growth, very likely by maintaining production and secretion of CPAF.

T932

549186-549277

Epistemic_statement

denotes

Understanding this chlamydial activity may help understanding persistent infection in vivo.

T933

549802-549871

Epistemic_statement

denotes

Nevertheless, SCV isolates could be distinguished by spa-typing, e.g.

T934

549916-550146

Epistemic_statement

denotes

Interestingly, Western blot analysis of protein A expression revealed that the truncated spa gene was associated with a protein of decreased size, and that two SCV isolates could be distinguished by increased protein A expression.

T935

550238-550368

Epistemic_statement

denotes

The results obtained indicated that increased SpA expression correlated with increased TLR2 activity and biofilm forming capacity.

T936

550753-550852

Epistemic_statement

denotes

However, we can only speculate that concomitant changes observed in the microbial environment (e.g.

T937

550853-551072

Epistemic_statement

denotes

infection and colonization with other microbial species), in the pulmonary and clinical status of the patient and in the antibiotic regimes may be responsible for the functional and genetic changes in the SCV phenotype.

T938

551219-551384

Epistemic_statement

denotes

Acinetobacter baumannii, an often multidrug-resistant nosocomial pathogen, may profit from motility during infection or while persisting in the hospital environment.

T939

551552-551660

Epistemic_statement

denotes

We could identify two akinetic mutants carrying transposon insertions in the dat and ddc gene, respectively.

T940

551913-552007

Epistemic_statement

denotes

The motility defect of both mutants could be cured by supplementing semi-solid media with DAP.

T941

552275-552340

Epistemic_statement

denotes

Current work aims at elucidating how DAP contributes to motility.

T942

552696-552793

Epistemic_statement

denotes

In addition, infections via vegetables are possible, as shown by the current outbreak in Germany.

T943

552918-553045

Epistemic_statement

denotes

To date, systematic therapy is hampered by the fact that the detailed mechanism of pathogenicity is still not fully understood.

T944

553046-553114

Epistemic_statement

denotes

EHEC express a number of factors that might contribute to virulence.

T945

553186-553338

Epistemic_statement

denotes

It has been shown that EspP might interact with hemostasis and immune response (1,2) but a systematic screening of relevant substrates is still lacking.

T946

554202-554387

Epistemic_statement

denotes

Altogether, it has been shown that EspP cleaves several physiologically relevant proteins in plasma as well as in platelets including protease inhibitors and surface adhesion molecules.

T947

554388-554530

Epistemic_statement

denotes

Further studies will elucidate the contribution of the newly identified substrates to the role of EspP as a possible virulence factor of EHEC.

T948

554997-555086

Epistemic_statement

denotes

However, the mechanism of translocation and post-translocation folding is not understood.

T949

555267-555435

Epistemic_statement

denotes

This suggests that unlike recessive mutations which affect recognition of the translocation machinery, the hlyA99 mutation interferes with some later step in secretion.

T950

555628-555848

Epistemic_statement

denotes

A second mutant (hlyAdel6), lacking the six C-terminal residues of HlyA, also showed reduced haemolytic activity and neither mutant protein regained normal haemolytic activity in in vitro unfolding/refolding experiments.

T951

555992-556106

Epistemic_statement

denotes

These results suggested that the mutations affected the correct folding of both HlyA and the betalactamase fusion.

T952

556107-556262

Epistemic_statement

denotes

Thus, we propose a dual function for the HlyA C terminus involving an important role in post-translocation folding as well as targeting HlyA for secretion.

T953

556382-556432

Epistemic_statement

denotes

However, not all fusions are secreted efficiently.

T954

556605-556782

Epistemic_statement

denotes

Anticipating that folding kinetics might be limiting, we introduced the 'folding' mutation Y283D into MalE and indeed the fusion protein was now secreted at a much higher level.

T955

558994-559207

Epistemic_statement

denotes

These results indicate that the LipA plays an important role in the regulation of the iron starvation sigma factor PvdS in P. aeruginosa thereby influencing the synthesis of pyoverdine and other virulence factors.

T956

559727-559826

Epistemic_statement

denotes

Proteases are enzymes that hydrolyze peptide bonds and can therefore degrade proteins and peptides.

T957

559827-559981

Epistemic_statement

denotes

As proteins are one of the basic building blocks in nature, proteases can influence a broad range of biological functions including the infection process.

T958

561175-561299

Epistemic_statement

denotes

SprP carries, in addition to its signal peptide and the S8 domain, a domain of unknown function (DUF) between both elements.

T959

562098-562179

Epistemic_statement

denotes

Initial results suggest a regulatory relationship in between these two proteases.

T960

562180-562296

Epistemic_statement

denotes

Finally, these results indicate that the two novel proteases, SprP and SprS, play a role in P. aeruginosa virulence.

T961

562476-562559

Epistemic_statement

denotes

The role of this molecule in the virulence of EHEC O157 is incompletely understood.

T962

563444-563579

Epistemic_statement

denotes

These data suggest that Iha plays dual roles in the virulence and/or fitness of EHEC O157:H7, as an adhesin and a siderophore receptor.

T963

564393-564560

Epistemic_statement

denotes

Therefore, proteolytic processing is of fundamental importance for Aap function, however, the underlying mechanisms and proteases involved have not been characterized.

T964

565094-565204

Epistemic_statement

denotes

Experiments using protease inhibitors suggest that Aap cleavage could also occur through additional proteases.

T965

565205-565349

Epistemic_statement

denotes

Our results indicate that S. epidermidis uses specific proteases for the controlled and coordinated processing and functional activation of Aap.

T966

565350-565569

Epistemic_statement

denotes

Given the importance of Aap-mediated S. epidermidis biofilm formation for pathogenesis of foreign-material associated infections our results could open new ways for the future development of therapeutic approaches, e.g.

T967

566064-566178

Epistemic_statement

denotes

It could be shown, that in in vitro systems an IDO activity inhibits the growth of bacteria, parasites or viruses.

T968

566379-566509

Epistemic_statement

denotes

Up to now, however, it remained unclear under which oxygen conditions IDO promotes its antimicrobial and immunoregulatory effects.

T969

566623-566735

Epistemic_statement

denotes

In recent studies we could show that the activity of IDO is inhibited under hypoxic conditions in vitro (1% O2).

T970

566941-567138

Epistemic_statement

denotes

We could find that the IDO-mediated inhibition of Staphylococcus aureus as well as group B Streptococcus growth was abrogated in IFN-stimulated human glioblastoma cells or HeLa-cells, respectively.

T971

567377-567573

Epistemic_statement

denotes

These findings indicate that the influence of the oxygen concentration on IDO function could be important for the defense against several pathogens that affect organs with different oxygen supply.

T972

567717-567913

Epistemic_statement

denotes

Only a few PLA are proven virulence factors 1,2 but the total number of known PLA is still limited and the details about host-pathogen interaction mechanisms involving PLA remain to be elucidated.

T973

567914-568056

Epistemic_statement

denotes

The opportunistic human pathogen Pseudomonas aeruginosa produces a variety of virulence factors; however, a PLA has not been described so far.

T974

568546-568652

Epistemic_statement

denotes

Subcellular localisation experiments revealed its association with the membrane fraction of P. aeruginosa.

T975

568653-568797

Epistemic_statement

denotes

More detailed localisation studies suggested that PlbF is most likely anchored to the bacterial inner membrane, as an integral membrane protein.

T976

569089-569211

Epistemic_statement

denotes

This motif is required for helix-helix interactions of inner membrane proteins, suggesting that PlbF may exist as a dimer.

T977

569501-569674

Epistemic_statement

denotes

Significant attenuation of the plbF negative mutant strain in killing of flies was observed confirming PlbF may represent a novel virulence factor produced by P. aeruginosa.

T978

569675-569898

Epistemic_statement

denotes

Further investigations of the cellular function of PlbF, particularly the relation of PlbF dimerisation and virulence of P. aeruginosa PAO1 might elucidate novel mechanisms of PLA-based pathogenicity mechanisms in bacteria.

T979

570694-571033

Epistemic_statement

denotes

Bioinformatic analyses of the staphylococcal met leader RNA revealed homologies and predicted structural elements associated with Bacillus T-box systems which represent terminator/antiterminator transcription control elements of Gram-positive bacteria that undergo conformational change upon specific binding of charged or uncharged tRNAs.

T980

571662-571883

Epistemic_statement

denotes

The pleiotropic repressor CodY seems to regulate the overall transcription of the T-box system, but does not interfere with the tight methionine-dependent regulation of the biosynthesis genes by the met leader RNA itself.

T981

572153-572298

Epistemic_statement

denotes

The combined data demonstrate that in staphylococci de novo methionine biosynthesis is obviously under the control of a T-box regulatory element.

T982

572299-572480

Epistemic_statement

denotes

This is unusual and in contrast to other Gram-positive bacteria which regulate this pathway mostly by S-box systems which represent S-adenosyl methionine (SAM)-binding riboswitches.

T983

572743-572819

Epistemic_statement

denotes

However, knowledge regarding its intracellular accommodation remains sparse.

T984

573825-573949

Epistemic_statement

denotes

SiiE of the SPI4 is necessary for adhesion to polarized epithelial cells whereas BapA was associated with biofilm formation.

T985

575285-575392

Epistemic_statement

denotes

One could conclude that BapA transcript underground degradation so that no signal can be observed using WB.

T986

575731-575821

Epistemic_statement

denotes

Altogether, these results showed that BapA may play a role in the surface of the bacteria.

T987

575822-575946

Epistemic_statement

denotes

Its secretion pattern depending on the time and medium conditions could suggest a protective function to the bacterial cell.

T988

575947-576109

Epistemic_statement

denotes

Further analysis of regulation of the expression and its possible role of invasion/adhesion is currently in progress to understand the role of BapA in host cells.

T989

576697-576808

Epistemic_statement

denotes

However, the underlying mechanism of Hp-induced epithelial barrier subversion is currently not well understood.

T990

577413-577504

Epistemic_statement

denotes

However, we identified HtrA as a secreted bacterial factor exhibiting proteolytic activity.

T991

578296-578413

Epistemic_statement

denotes

We assume that blocking of HtrA activity might help combat Hp persistence in the early phases of bacterial infection.

T992

578863-578939

Epistemic_statement

denotes

fRMsr has been previously shown to be specific for free Met-R-SO in E. coli.

T993

581044-581393

Epistemic_statement

denotes

Recently, we showed that high intracellular amounts of the secondary messenger c-di-GMP in S. typhimurium abolished stimulation of a pro-inflammatory immune response and inhibition of invasion of the gastrointestinal epithelial cell line HT-29 suggesting regulation of transition between biofilm formation and virulence by c-di-GMP in the intestine.

T994

581764-581913

Epistemic_statement

denotes

Inhibition of the invasion phenotype by c-di-GMP is associated with inhibition of secretion of the type three secretion system effector protein SipA.

T995

582287-582450

Epistemic_statement

denotes

A. Lüttich* 1 , S. Brunke 1,2 , I. Jacobsen 1 Candida albicans is both a successful commensal and a pathogen of humans that can infect a broad range of body sites.

T996

582451-582606

Epistemic_statement

denotes

During the infection process, C. albicans has the potential to adapt to different host niches and to survive the attack of phagocytes, such as macrophages.

T997

582607-582691

Epistemic_statement

denotes

Previous evidence suggests that microevolution plays a central role in this process.

T998

583061-583199

Epistemic_statement

denotes

Using this system, we also investigated whether C. albicans can utilise alternative signal transduction pathways under selective pressure.

T999

583601-583741

Epistemic_statement

denotes

We therefore chose this strain for further investigation and monitored its adaptation to macrophages during a series of co-culture passages.

T1000

583920-584107

Epistemic_statement

denotes

Surprisingly, the strain was also now able to form filaments under other conditions and, in contrast to the original efg1/cph1 mutant, has regained the ability to invade epithelial cells.

T1001

584197-584363

Epistemic_statement

denotes

The phenotype was stable in the absence of selective pressure, indicating that microevolutionary events have bypassed the reliance on Cph1 and Efg1 for filamentation.

T1002

584460-584668

Epistemic_statement

denotes

These and further investigations of the genetic cause of the adaptation will yield insights into the genomic and genetic plasticity of this important fungal pathogen during adaptation to specific host niches.

T1003

584669-584896

Epistemic_statement

denotes

A. Koenigs* 1 , C. Hammerschmidt 1 , D. Barthel Introduction: Borrelia burgdorferi, the etiological agent of Lyme disease exploits an array of strategies in order to overcome the host immune response and establish an infection.

T1004

585121-585232

Epistemic_statement

denotes

OspA, OspC, CspA, ErpA, ErpC, and ErpP have previously been identified as ligands for host-derived plasminogen.

T1005

585407-585655

Epistemic_statement

denotes

To verify whether bound plasminogen/plasmin is proteolytically active, we performed substrate degradation assays utilizing both a chromogenic substrate, D-valyl-leucyl-lysine-pnitroanilidedihydrocholride as well as the natural substrate fibrinogen.

T1006

586626-586816

Epistemic_statement

denotes

By utilizing several plasminogen constructs containing single or multiple Kringle domains, it was determined that the Kringle domain 4 most likely represents the major BopA interaction site.

T1007

587173-587328

Epistemic_statement

denotes

Binding of plasminogen/plasmin might endow B. burgdorferi with the capability to resist opsonization and to degrade components of the extracellular matrix.

T1008

587715-587838

Epistemic_statement

denotes

A limitation of this model is the restricted dimensionality which contrasts three dimensional (3D) host tissue environment.

T1009

587839-588118

Epistemic_statement

denotes

Using a 3D collagen gel setup (3D-CoG), it has been shown that Yersinia enterocolitica as a prototype of an extracellularly replicating pathogen exhibits unusual growth behaviour in this system, resembling in vivo microcolony formation in infected tissues (Freund et al., 2008) .

T1010

588119-588275

Epistemic_statement

denotes

Here we present first results of the growth behaviour of Staphylococcus aureus and its interaction with neutrophils in this model using confocal microscopy.

T1011

588399-588506

Epistemic_statement

denotes

In a first approach we compared the growth behavior of strain Newman and the derived mutants saeRS and ica.

T1012

588507-588658

Epistemic_statement

denotes

Surprisingly, we found that strain Newman and both mutants formed bacterial clusters similar to those observed in cell culture medium without collagen.

T1013

590031-590188

Epistemic_statement

denotes

Fusion with lysosomes is avoided, but LCVs acquire endosomal markers and associate with mitochondria, early secretory vesicles and the endoplasmic reticulum.

T1014

590418-590640

Epistemic_statement

denotes

The identification of the biochemical and cellular function of some of these Icm/Dot substrates is challenging, as the deletion of single or multiple effectors in many cases does not show an intracellular growth phenotype.

T1015

591326-591515

Epistemic_statement

denotes

First results indicate a high overlap of identified host proteins, yet also reveal a number of small GTPases and other host proteins that previously have not been identified as LCV markers.

T1016

592295-592539

Epistemic_statement

denotes

Pulldown experiments with PI lipids coupled to agarose beads revealed that L. longbeachae SidC also specifically binds to PI(4)P. L. pneumophila modifies the PI pattern of LCVs in an Icm/Dot dependent manner, yet the mechanism remained elusive.

T1017

592540-592839

Epistemic_statement

denotes

We recently discovered a bacterial PI phosphatase, which is translocated into the host via the Icm/Dot T4SS and preferentially hydrolyses poly-phosphorylated PIs yielding PI(4)P. This PI phosphatase, termed LppA, might shape the LCV PI pattern to promote binding of L. pneumophila effector proteins.

T1018

594026-594282

Epistemic_statement

denotes

We could demonstrate that glycosaminoglycans (GAGs) on host cell surfaces are involved in attachment and subsequent infection by C. pneumoniae and that the bacterial surface-associated OmcB protein is the GAG-binding adhesin (Moelleken and Hegemann 2008) .

T1019

594447-594565

Epistemic_statement

denotes

In adhesion studies, using purified recombinant Pmp21 protein, we were able to show that it could bind to human cells.

T1020

595273-595390

Epistemic_statement

denotes

Through mass spectrometry we identified the epidermal growth factor receptor (EGFR1) as a potential target for Pmp21.

T1021

595581-595753

Epistemic_statement

denotes

Most importantly a knockdown of EGFR resulted in a diminished binding of fluorescently labeled bacteria, indicating that EGFR indeed serves as a receptor for C. pneumoniae.

T1022

595754-595909

Epistemic_statement

denotes

Vice versa we could enhance the infection approximately by the factor two, when we overexpressed EGFR in cells deficient for this receptor tyrosine kinase.

T1023

596360-596497

Epistemic_statement

denotes

The obligate intracellular bacteria, Chlamydia trachomatis (C. trachomatis), however evolved mechanisms to use ROS for its own advantage.

T1024

596718-596905

Epistemic_statement

denotes

Despite the positive effect of ROS on chlamydial development, it is incompletely understood how different cellular conditions that lead to altered ROS production affect chlamydial growth.

T1025

597676-597941

Epistemic_statement

denotes

Consequent host cell signaling changes were followed by detection of hypoxia inducible factor, HIF-1 stabilization and phosphorylation of the acetyl-coenzym Acarboxylase (ACC) enzyme that might mediate the host cell metabolic changes that support chlamydial growth.

T1026

598455-598589

Epistemic_statement

denotes

This organelle trafficking might escort the perinuclear clustering of inflammasomes that is required for their ROS-induced activation.

T1027

599301-599429

Epistemic_statement

denotes

The possible interaction between these two types of pathogens and its influence on their fate inside host cell is still unknown.

T1028

599805-599879

Epistemic_statement

denotes

Interestingly, C. trachomatis favored enhanced entry and survival of HHV6.

T1029

599880-600052

Epistemic_statement

denotes

In a co-infection model, both pathogens affected each other's entry, survival as well as infectivity and influenced the replication and transcription pattern of each other.

T1030

600472-600608

Epistemic_statement

denotes

Vienna, Department of pathobiology, Vienna, Oesterreich As mycoplasmas are poorly understood pathogens, they are difficult to eradicate.

T1031

600609-600825

Epistemic_statement

denotes

Despite considerable advances in the area of mycoplasma molecular genetics in the past decade, progress towards understanding their pathogenicity mechanisms is hindered by the paucity of available genetic tools (1) .

T1032

600826-601045

Epistemic_statement

denotes

Mycoplasma agalactiae (MA) is an important ruminant pathogen for which the pathogenicity mechanisms are largely unknown, mainly because of the previous incapability to genetically manipulate it until the year 2005 (2) .

T1033

601277-601604

Epistemic_statement

denotes

For the functional analysis of MA genes, the Tn mutants were subjected to several in vitro screening protocols, especially to those which could have a direct role in its pathogenicity, such as biofilm formation, growth, adherence and antibiotic sensitivity, in order to shortlist them for an experimental sheep infection study.

T1034

601822-602002

Epistemic_statement

denotes

Although reported for some mycoplasmas, direct genomic sequencing and other methods to sequence the Tn insertion sites are not always successful, or are rather costly or laborious.

T1035

603260-603345

Epistemic_statement

denotes

Moreover, ULVWF is considered as a potential binding partner for pathogenic bacteria.

T1036

603346-603471

Epistemic_statement

denotes

It is worth to emphasize that ULVWF fibers can be formed on an intact endothelial cell layer, independent of vascular damage.

T1037

603472-603573

Epistemic_statement

denotes

Previous studies indicate that Staphylococcus aureus binds to VWF via staphylococcal protein A (SpA).

T1038

603574-603633

Epistemic_statement

denotes

However, the influence of ULVWF fibers is not known so far.

T1039

604205-604442

Epistemic_statement

denotes

To prove whether the binding of S. aureus to the endothelium is specifically mediated by ULVWF we used in some experiments the specific VWF degrading protease ADAMTS-13 (a disintegrin and metalloproteinase with thrombospondin motifs 13).

T1040

604555-604673

Epistemic_statement

denotes

SpA supported the binding of S. aureus mainly to the globular form of VWF which is in agreement with previous studies.

T1041

605116-605273

Epistemic_statement

denotes

Discussion: Within the context of clinical studies a significant contribution of VWF and ADAMTS-13 to vascular disease progression has been shown previously.

T1042

605507-605609

Epistemic_statement

denotes

Our data suggest an adhesion mechanism independent of secreted factors or surface associated adhesins.

T1043

605610-605752

Epistemic_statement

denotes

However, the acting molecular mechanism that triggers strong binding of S. aureus to ULVWF is currently unknown and requires further research.

T1044

608459-608657

Epistemic_statement

denotes

H. Büttner 1 , M. Christner 1 , H. Rohde* Medizinische Mikrobiologie, Virologie und Hygiene, Hamburg, Deutschland Staphylococcus epidermidis is a leading cause of foreign body associated infections.

T1045

610652-610808

Epistemic_statement

denotes

Therefore, as heparin specifically binds to FnIII 12, this particular domain is obviously crucial for Embp mediated S. epidermidis adherence to fibronectin.

T1046

610998-611110

Epistemic_statement

denotes

The underlying molecular basis of Embp -fibronectin interactions involves a novel, so far undescribed mechanism.

T1047

611282-611422

Epistemic_statement

denotes

Ceramide, a bioactive sphingolipid involved in cell signalling, has been shown to assemble along the cell membrane of the airway epithelium.

T1048

611534-611642

Epistemic_statement

denotes

Accumulation of domains has been directly correlated with patient maturation and vulnerability to infection.

T1049

611643-611773

Epistemic_statement

denotes

Increased assemblages of ceramide are a molecular outlier of patients with CF and act as potential stages for aberrant signalling.

T1050

611774-611993

Epistemic_statement

denotes

In this study we show that although commonly found along the basal lateral membrane, Beta 1 integrin maintains a permanent position on ceramide enriched domains on the luminal side of airway epithelial cells in CF mice.

T1051

612565-612770

Epistemic_statement

denotes

Our data indicates that ceramide enriched domains, and the Beta 1 integrin molecules they host, play an important role in the virulence of P. aeruginosa within the airways of patients with Cystic Fibrosis.

T1052

612906-613169

Epistemic_statement

denotes

These two findings suggest the RGD binding domain of Beta 1 integrin may act as an adherence mechanism for P. aeruginosa and that increased clustering of this receptor in patients with CF may play an important role in the infectious manifestations of the disease.

T1053

613170-613269

Epistemic_statement

denotes

Preliminary data indicates inhalation of RGD peptides may be a novel treatment option for patients.

T1054

613465-613664

Epistemic_statement

denotes

Paraffin embeded tissue (A,B,C) and in situ stained paraffin embedded tissue (D,E) The type three secretion system (TTSS) of Yersinia enterocolitica (Ye) is crucial to evade the host immune response.

T1055

614643-614891

Epistemic_statement

denotes

After infection with a YadA mutant no Yop injection could be detected while a Inv mutant showed nearly similar Yop injection as a wildtype strain, indicating that YadA but not Inv is crucial for Yop injection into leukocytes during mouse infection.

T1056

615352-615483

Epistemic_statement

denotes

Inv mediated Yop injection into leukocytes in contrast to YadA mediated Yop injection can occur in a 1 integrin independent manner.

T1057

617681-618128

Epistemic_statement

denotes

To investigate the disruption of the brush border of polarized epithelial cells, SL1344 wild-type (WT), sipA, sopA, sopB, sopE, sopE2mutant strains, M712 strain, which lacks the five mentioned effector proteins, and their complemented derivates were used for invasion experiments in MDCK Pf and C2bbe1 cell lines, the later were also used to evaluate the disruption of the trans-epithelial electrical resistance (TEER) by the Salmonella infection.

T1058

621145-621358

Epistemic_statement

denotes

Furthermore, in comparative radioactive binding assays using human or canine plasminogen, no differences in quality of interaction could be observed, a prerequisite for establishing infections across host species.

T1059

622365-622599

Epistemic_statement

denotes

Furthermore, electron microscopic illustration and time lapse imaging demonstrated plasmin-mediated transmigration of fibrinous thrombi by S. canis and, therefore, may represent a mechanism for bacterial dissemination within the host.

T1060

622600-622717

Epistemic_statement

denotes

Discussion: Although S. canis is a zoonotic pathogen, very little is known about its virulence factors or mechanisms.

T1061

622882-622985

Epistemic_statement

denotes

However, binding of SCM to mPlg presents a mechanistically different bacterial-plasminogen interaction.

T1062

622986-623091

Epistemic_statement

denotes

The role of such interactions in the etiopathogenesis of these infections requires further investigation.

T1063

623092-623284

Epistemic_statement

denotes

Burkholderia pseudomallei, the etiological agent of melioidosis, and Burkholderia thailandensis are closely related organisms mainly found in the soil in Southeast Asia and Northern Australia.

T1064

623620-623774

Epistemic_statement

denotes

The Burkholderia T6SSs present in a genome are evolutionarily distinct, leading us to hypothesize that each secretion system performs a discrete function.

T1065

624003-624177

Epistemic_statement

denotes

This is likely due to a specific role T6SS-5 plays in the subversion of or resistance against MyD88 dependent immune response since T6SS-5 is highly virulent in MyD88 -/mice.

T1066

624719-624816

Epistemic_statement

denotes

Data on T6S substrates are scarce and no Burkholderia T6S effectors have been identified to date.

T1067

625295-625450

Epistemic_statement

denotes

Interestingly, VgrG-5 contains a putative C terminal effector domain that does not display significant sequence similarity to proteins with known function.

T1068

625625-625834

Epistemic_statement

denotes

Together the data suggest an important role of Burkholderia T6S in determining the outcome of an infection by directly targeting eukaryotic host cells or by allowing the bacteria to persist in the environment.

T1069

626940-627013

Epistemic_statement

denotes

Furthermore, the shikimate pathway could be determined by GC/MS analysis.

T1070

627735-627817

Epistemic_statement

denotes

However, the isotopologue profiles of these mutants were similar to the wild-type.

T1071

628356-628575

Epistemic_statement

denotes

Recently, we could show that FPR2 is crucial for recruiting and activating PMN in staphylococcal infections, because it senses concentrations of the major staphylococcal cytolysins phenol-soluble modulin (PSM) peptides.

T1072

629121-629179

Epistemic_statement

denotes

This effect could be inhibited by the FPR2antagonist WRW4.

T1073

629491-629589

Epistemic_statement

denotes

However, both species activated the FPR2 paralog FPR1, which senses bacterial formylated peptides.

T1074

629590-629817

Epistemic_statement

denotes

The enterococcal genomes do not encode peptides with apparent similarity to PSM peptides and no peptides with PSM-like properties could be identified in enterococcal culture supernatants in sufficient quantitites for detection.

T1075

629818-630095

Epistemic_statement

denotes

To further characterize the unknown FPR2 ligands produced by E. faecium supernatants were treated with proteases, which completely abolished the ability to stimulate FPR2 transfected HL-60 cells thereby indicating that the unknown FPR2 ligands of E. faecium represent peptides.

T1076

630260-630668

Epistemic_statement

denotes

Structure-function relationship of zwitterionic cell wall polymer dependent immune modulatory mechanisms C. Weidenmaier* 1 , S. Wanner 1 , M. Rautenberg 1 , S. Baur 1 , L. Kull 1 1 Universität Tübingen, IMIT, Tübingen, Deutschland Recent advances on the field of glycobiology led to discovery of novel mechanisms by which bacterial cell wall glycopolymers can directly modulate the host immune response (1) .

T1077

630889-631101

Epistemic_statement

denotes

We could recently show that the important pathogenicity factor (2) cell wall teichoic acid (WTA) of S. aureus has a similar activity and is able to activate CD4-T cells in an MHCII presentation depended way (3) .

T1078

631190-631538

Epistemic_statement

denotes

Interestingly mostly pathogenic Gram-positive bacterial species seem to exhibit the ribitol-Pi repeating units with D-alanine (however WTA structures differ in side chain sugar composition or contain additional repeating unit sugars), whereas non pathogenic species often have shorter glycerol-Pi repeating units or no D-alanine modifications (1) .

T1079

632082-632223

Epistemic_statement

denotes

It is not known so far whether the amount of teichoic acids differs during the development of an infection or even between bacterial strains.

T1080

632224-632339

Epistemic_statement

denotes

Interestingly, we find that highly pathogenic S. aureus strains exhibit an elevated WTA amount in their cell walls.

T1081

632340-632631

Epistemic_statement

denotes

Purified protein-free cell wall fractions from these strains induce T cell proliferation and cytokine production more efficiently than cell wall from less pathogenic strains In addition we could demonstrate that cell wall fractions of these strains are more active in skin abscess formation.

T1082

633173-633308

Epistemic_statement

denotes

S. aureus colonization of undomesticated sub-Saharan animals could pose a risk for inter-species transmission and infections in humans.

T1083

633309-633506

Epistemic_statement

denotes

We therefore characterize S. aureus isolates from wild and captive animals from sub-Saharan Africa to obtain data for further investigations of cross-species transmission of S. aureus in this area.

T1084

634298-634486

Epistemic_statement

denotes

Resistance to penicillin, tetracycline and cotrimoxazole was 12%, 6% and 1%, respectively and was significantly associated with captive animals (OR = inf., 95% CI = 32.48-inf., p < 0.001).

T1085

635194-635302

Epistemic_statement

denotes

Conclusion: Our results suggest that colonization of human and nonhuman primates with S. aureus is frequent.

T1086

635432-635530

Epistemic_statement

denotes

This will provide an excellent tool to investigate potential cross-species transmission in future.

T1087

637852-637975

Epistemic_statement

denotes

But regarding international data there is an urgent need of active surveillance on carbapenem-resistant Enterobacteriaceae.

T1088

637976-638154

Epistemic_statement

denotes

Both local reports and linked data of national and international surveillance networks may be successful approaches to an effective containment of these multi-resistant bacteria.

T1089

638591-638655

Epistemic_statement

denotes

Roe deer and red deer are regarded as potential reservoir hosts.

T1090

638656-638831

Epistemic_statement

denotes

Considerable strain variation has been suggested to occur within this species, because isolates from humans and animals differed in their pathogenicity for heterologous hosts.

T1091

639008-639117

Epistemic_statement

denotes

237 samples from humans, domestic animals, potential reservoir hosts, and Ixodes ricinus ticks were analyzed.

T1092

639187-639269

Epistemic_statement

denotes

eBURST analysis revealed one clonal complex with sequence type (ST) 55 as founder.

T1093

639417-639496

Epistemic_statement

denotes

All samples from the US were ST 64, what might reflect their geographic origin.

T1094

639687-639824

Epistemic_statement

denotes

As A. phagocytophilum strains infecting humans, dogs and horses belonged to one clonal complex, they seem to share the same epidemiology.

T1095

639923-640185

Epistemic_statement

denotes

Because the concatenated sequences from I. ricinus ticks are found in both clusters, they might be involved in the transmission cycle of A. phagocytophilum strains that infect humans and domestic animals (cluster 1) and of those that infect roe deer (cluster 2).

T1096

640186-640380

Epistemic_statement

denotes

In contrast to red deer, roe deer are probably not the reservoir for granulocytic anaplasmosis in humans and domestic animals, as their concatenated sequences formed a clearly separated cluster.

T1097

640643-640868

Epistemic_statement

denotes

Especially for the delineation of extraintestinal pathogenic Escherichia coli (ExPEC) and commensal E.coli this is a challenging task, because certain ExPEC and commensal E.coli strains may be geno-and phenotypically similar.

T1098

641320-641429

Epistemic_statement

denotes

Furthermore, we evaluated how additional markers improve the discriminatory potential of both typing methods.

T1099

642540-642673

Epistemic_statement

denotes

However, the exact mode of transmission of this typically food-borne pathogen in that particular part of the world is widely unknown.

T1100

644077-644353

Epistemic_statement

denotes

Eight S. enterica isolates that were isolated from one particular well were discriminated to 7 distinct clones by PFGE thus demonstrating that a single well can be colonized by different S. enterica strains and that individual clones can persist about several weeks in a well.

T1101

644354-644475

Epistemic_statement

denotes

Discussion: PFGE data from the blood culture isolates indicate that endemic clones circulate within the local population.

T1102

644620-644789

Epistemic_statement

denotes

The interpretation is limited because different distinct serotypes may colonize a well at the same time while only one individual clone was selected per isolation event.

T1103

644790-644985

Epistemic_statement

denotes

The high number of isolates from the wells with no matches to blood culture isolates during the whole study interval is more likely to support the hypothesis of alternative modes of transmission.

T1104

644986-645089

Epistemic_statement

denotes

Further studies addressing the role of food for the transmission of S. enterica in Ghana should follow.

T1105

645648-645758

Epistemic_statement

denotes

Although the WHO region Europe has been certified polio-free in 2002, the risk of reintroduction remains (e.g.

T1106

646229-646445

Epistemic_statement

denotes

In this context the enterovirus surveillance system was extended and can now be used for both, the enterovirus diagnostics in patients with aseptic meningitis / encephalitis and patients with acute flaccid paralysis.

T1107

648188-648608

Epistemic_statement

denotes

Characterization of extended spectrum -lactamase producing Escherichia coli: comparison of phylogenetic grouping by the DiversiLab system, mononucleotide motifs and genetic markers T. Vollmer* 1 , C. Knabbe 1 , J. Dreier Bad Oeynhausen, Deutschland Introduction: Rapid and reliable methods to identify the molecular relatedness in clinical isolates are essentially needed to investigate potential routes of transmission.

T1108

648609-648779

Epistemic_statement

denotes

Randomly amplified polymorphic DNA amplification (RAPD) techniques have been shown as a useful and comparatively simple tool for the discrimination of strain relatedness.

T1109

650198-650272

Epistemic_statement

denotes

ESBL-typing by these three different methods showed excellent correlation.

T1110

650553-650717

Epistemic_statement

denotes

Further investigations include the evaluation of the DL with an in house automated RAPD-PCR using different established primers followed by chip-gelelectrophoresis.

T1111

652321-652422

Epistemic_statement

denotes

The data suggest that bactericidal antibodies will be effective only on a subset of cnl meningococci.

T1112

652619-653001

Epistemic_statement

denotes

C. Rohde* 1 , K. Selezska 2 , M. Kazmierczak 1,3 , J. Sikorski 1, 3, 4 1 DSMZ, Mikrobiologie, Braunschweig, Deutschland 2 HZI, Braunschweig, Deutschland 3 DSMZ, Braunschweig, Deutschland 4 Deutschland Introduction:The lytic potential of novel Pseudomonas aeruginosa (PA) phages against a large number of novel environmental and clinical PA isolates was challenging to be studied 1.)

T1113

653091-653287

Epistemic_statement

denotes

to find a possible relationship between lysis phenomena in the phylogenetic tree of these hosts and the allocation of clusters of lysed strains: a phylogenetic approach using lysis as "phenotype".

T1114

653288-653434

Epistemic_statement

denotes

The latter addresses the potential role of phages in the microevolutionary diversification of PA strains into different genetic lineages (clades).

T1115

653493-653584

Epistemic_statement

denotes

The large pool of new hosts and phages offered a test system to respond to these questions.

T1116

654744-654799

Epistemic_statement

denotes

All results finally suggest two unrelated phage groups.

T1117

654910-654962

Epistemic_statement

denotes

Lysis phenotypes appeared to depend on the serotype.

T1118

654963-655101

Epistemic_statement

denotes

Some serotypes showed large proportions of full lysis, others appeared to confer phage resistance, some were sensitive only to few phages.

T1119

655419-655569

Epistemic_statement

denotes

Conclusion: From the phage lysis patterns we conclude there is therapeutic potential of some of these highly lytic phages with broad PA host spectrum.

T1120

655570-655930

Epistemic_statement

denotes

From the lysis phenotypes we conclude that phages, via the diversity of host receptor types, have potential to contribute to the intraspecies microevolutionary diversification within PA. From additional own studies (not shown) we have reasons to believe that the population dynamics of PA were probably shaped by environmental forces, not by clinical habitats.

T1121

656096-656337

Epistemic_statement

denotes

Friedrich 1 1 University Medical Center Groningen, Medical Microbiology, Groningen, Niederlande Background: Methicillin-resistant Staphylococcus aureus (MRSA) is an increasing health problem in both hospital and community settings worldwide.

T1122

656601-656770

Epistemic_statement

denotes

Although, several PCR-based procedures were designed for typing the SCCmec cassettes, they were often found to be limited in their ability to characterize MRSA isolates.

T1123

656771-656934

Epistemic_statement

denotes

The goal of our study was to compare the SCCmec typing results produced by well-established multiplex-PCR protocol with those obtained by a microarray-based assay.

T1124

657477-657623

Epistemic_statement

denotes

Results: Using the multiplex-PCR protocol, 179 MRSA isolates were typeable whereas from 27 MRSA isolates, the SCCmec type could not be determined.

T1125

658594-658763

Epistemic_statement

denotes

Conclusions: The microarray approach appeared to be more efficient than the PCR-based protocol in identification of SCCmec types among genetically diverse MRSA isolates.

T1126

658764-658922

Epistemic_statement

denotes

Moreover, the microarray-based method is an inexpensive and fast procedure, and can be easily implemented for investigations in routine clinical laboratories.

T1127

659918-660178

Epistemic_statement

denotes

For several years now increasing infection rates of immunocompromized adult patients have been reported In rare cases an infection in neonates, pregnant women and immunocompromized elderly patients can lead to a toxic shock syndrome with necrotizing fasciitis.

T1128

660308-660460

Epistemic_statement

denotes

It is typically caused by Streptococcus pyogenes and mutations of a general virulence regulator (cov) have been reported in association with STSS cases.

T1129

661447-661598

Epistemic_statement

denotes

The two component cov regulator represses hemolysis and the mutation was associated with an increased hemolysis and pigmentation in the mutated strain.

T1130

661599-661673

Epistemic_statement

denotes

Another strain harbored a 3 bp deletion that had previously been reported.

T1131

661848-662030

Epistemic_statement

denotes

In conclusion virulence regulator gene mutations in strains causing streptococcal toxic shock syndrome as they have been described for S. pyogenes can also be found in S. agalactiae.

T1132

662031-662259

Epistemic_statement

denotes

A detailed molecular epidemiologic characterization of STSS S. agalactiae strains by MLST, capsular typing and surface protein determination showed them to be heterogenous, despite a certain predominance of ST1 and ST23 strains.

T1133

662754-662913

Epistemic_statement

denotes

Recently, an outbreak of a novel clone of E. coli bearing the rare serotype O104:H4 has threatened Northern Germany and challenged the health care authorities.

T1134

663657-663746

Epistemic_statement

denotes

Interestingly, EPEC were not only found in young children, but in adult patients as well.

T1135

663814-663991

Epistemic_statement

denotes

The E. coli species responsible for the recent outbreak bears a combination of pathogenic factors that has not been found in our 20,000 stool probes during the past three years.

T1136

663992-664230

Epistemic_statement

denotes

Discussion: According the microbiologic-infectiologic quality standards (MIQ) of the German Society for Hygiene and Microbiology, screening of stool samples for pathogenic E. coli species should only be performed under certain conditions.

T1137

664231-664335

Epistemic_statement

denotes

Following this standard, EHEC, STEC, EAEC and EPEC would not have been detected in most of our patients.

T1138

664336-664506

Epistemic_statement

denotes

For example, the MIQ standard only considers EPEC a causative agent in adult patients if they are immunocompromised or have persisting diarrhea for more than three weeks.

T1139

664507-664547

Epistemic_statement

denotes

Our data contradict this recommendation.

T1140

665815-665996

Epistemic_statement

denotes

In the present study, we investigated whether sand flies are prevalent in Bavaria and whether wild mice carry Leishmania parasites and therefore might function as reservoir animals.

T1141

666660-666763

Epistemic_statement

denotes

However, until now the involved hypothetical intermediate SF O157:H7 clone had not yet been identified.

T1142

667702-667804

Epistemic_statement

denotes

Of these, certain SNPs or SNP genotypes could be determined to differentiate each serotype or cluster.

T1143

667805-667925

Epistemic_statement

denotes

Interestingly, SNP data enabled us to further differentiate amongst EHEC O157 subgroups, especially within EHEC O157:H7.

T1144

668034-668172

Epistemic_statement

denotes

The SNP data was further investigated to elaborate new typing techniques using fewer loci in order to get a comparable rate of resolution.

T1145

668594-668772

Epistemic_statement

denotes

In summary, SNP-based typing of EHEC O55 and O157enabled us to close the gap within the evolutionary model of EHEC O157 by identification of an isolate of the hypothetical clone.

T1146

668773-669011

Epistemic_statement

denotes

Moreover, the identified SNPs and associated genotypes open up new prospects and challenges to develop alternative typing methods with less costs and comparable rates of resolution for epidemiological investigations and phylogeny studies.

T1147

669206-669370

Epistemic_statement

denotes

At present, MRSA is one of the major causes of wound infections in small animals and horses, and infected animals may provide a significant threat to public health.

T1148

669371-669519

Epistemic_statement

denotes

Based on these findings, the aim of this study was to determine the proportion of LA-MRSA in wound swabs obtained from companion animals in Germany.

T1149

670186-670287

Epistemic_statement

denotes

Interestingly, the proportion of spa-types frequently associated with livestock-associated MRSA (e.g.

T1150

670633-670841

Epistemic_statement

denotes

A similar trend was seen in wound infections due to MRSA in dogs, which in the past had frequently been associated with CC22-and CC5-strains, while currently we identified several cases associated with CC398.

T1151

670842-671237

Epistemic_statement

denotes

Conclusion: The detected proportions of CC398-associated MRSA in horses and dogs suggests a rapid spread of LA-associated strains into animals other than livestock and raise the question whether these EHSG-MRSA may harbour certain factors or abilities (genetic and/ or functional) mediating the obvious successful spread among different mammalian species apart from their methicillin-resistance.

T1152

671777-671973

Epistemic_statement

denotes

Two pilus regions have been identified in the pneumococcal genome: PI-1 (Pilus Islet-1) and PI-2 (Pilus Islet-2) and, at least for PI-1, their role in pneumococcal pathogenesis has been suggested.

T1153

672808-672928

Epistemic_statement

denotes

Surprisingly, the majority (71,4%) of the pilus-positive non-invasive isolates were positive for both pneumococcal pili.

T1154

673360-673543

Epistemic_statement

denotes

The clonality of the pilus-containing isolates identified here is being determined by MLST analysis and their correlation with antibiotic resistance profiles will also be established.

T1155

673544-673746

Epistemic_statement

denotes

Finally, these data show the scenario of pneumococcal pili distribution among pneumococcal clinical isolates in Germany and may support the potential of PI-1 and PI-2 constituents as vaccine candidates.

T1156

673747-673883

Epistemic_statement

denotes

Background: Hospital-acquired methicillin resistant Staphylococcus aureus (HA-MRSA) is a growing public health concern across the world.

T1157

673884-673944

Epistemic_statement

denotes

Early detection of clusters is vital for patient protection.

T1158

673945-674210

Epistemic_statement

denotes

Pulsed-field gel electrophoresis (PFGE) is considered a 'gold standard' in detecting important outbreak events and widely used despite several limitations such as limited resolution and lack of digitized data, making intra-and interlaboratory comparisons difficult.

T1159

674211-674484

Epistemic_statement

denotes

Spa typing, which relies on sequence variation within the S. aureus protein A gene (spa), has been proven to be a successful tool for investigating the relatedness of strains and the sequence data is easily stored in databases and communicated between researchers globally.

T1160

674572-674813

Epistemic_statement

denotes

These maps can distinguish chromosomal events that are ~>1.5 kb in size, providing a higher resolution of data, as well as fragment organization within the genome, as compared to PFGE (~30 kb detection limit) and probably also to spa typing.

T1161

675212-675369

Epistemic_statement

denotes

The remaining two isolates were different spa types, yet one had the same sequence type (multilocus sequence typing), as the epidemiologically related group.

T1162

675739-675916

Epistemic_statement

denotes

The three unrelated isolates with identical spa types were more closely related to the epidemiologically-linked group (though not identical) than the 2 with different spa types.

T1163

676305-676448

Epistemic_statement

denotes

OM data corresponded with both the PFGE and spa typing results, yet with a higher resolution, providing more detailed phylogenetic information.

T1164

676449-676643

Epistemic_statement

denotes

This increased resolution may be useful in tracking the progress of a cluster, though further investigations are needed to verify that OM alone is sufficient to identify the spread of pathogens.

T1165

676644-677196

Epistemic_statement

denotes

M. Merker* 1 , T. Kohl 2 , J. Kalinowski 2 , S. Ruesch-Gerdes 3 , L. Truebe 1 , A. Roetzer 1 , S. Niemann 1 1 Forschungszentrum Borstel, Molekulare Mykobakteriologie, Borstel, Deutschland 2 University of Bielefeld, CEBITEC, Bielefeld, Deutschland 3 Forschungszentrum Borstel, National Reference Center for Mycobacteria, Borstel, Deutschland Background: Transmission and phylogenetic background of clinical Mycobacterium tuberculosis complex isolates can be analyzed by genotyping techniques (IS6110 DNA fingerprinting, spoligotyping, MIRU-VNTR typing).

T1166

678430-678574

Epistemic_statement

denotes

Interestingly, the emergence of SNPs in resistance genes coincides with the development of phenotypic resistance within the course of treatment.

T1167

678782-678909

Epistemic_statement

denotes

Conclusions: Our results reveal a striking diversity in serial patient isolates that cannot be captured by standard genotyping.

T1168

678939-679035

Epistemic_statement

denotes

as additional resistance mechanisms or compensatory evolution are currently under investigation.

T1169

679044-679112

Epistemic_statement

denotes

Therefore the existence of two different pathovars was hypothesized.

T1170

679572-679718

Epistemic_statement

denotes

The 231 bi-allelic polymorphisms were used to construct a minimum spanning tree (MST) which was associated in 86 haplotypes among the 102 strains.

T1171

679719-679850

Epistemic_statement

denotes

Results indicate that two subpopulations have evolved into different pathovars that are associated with distinct clinical pictures.

T1172

679851-680200

Epistemic_statement

denotes

In addition we could show that much of the population structure of ST121 is local, largely endemic and spread to other countries or continents occur only on rare occasions.Furthermore, and in agreement to prior results in ST5, ST22 and ST239, mapping of spa types onto the MST revealed several spa types whose patterns seemed to reflect homoplasies.

T1173

680390-680585

Epistemic_statement

denotes

It is currently unclear, however, whether genomic variation may also enable the reconstruction of transmission chains between individual patients, e. g. during an outbreak of hospital infections.

T1174

681125-681320

Epistemic_statement

denotes

However, not each and every patient got infected by a unique MRSA, and MRSA genomes from several patients were indistinguishable or very closely related, suggesting potential transmission events.

T1175

681321-681430

Epistemic_statement

denotes

It appears that genome sequencing holds promising potential for tracing MRSA spatial spread at a local scale.

T1176

681562-681721

Epistemic_statement

denotes

In Germany, screening is recommended based on the guidelines of the Robert-Kochinstitute; yet, the screening intensity is largely varying between institutions.

T1177

682712-682904

Epistemic_statement

denotes

These figures are higher than those previously determined in other German APS programs, and they also differ from those previously reported from other central European regions or institutions.

T1178

682905-683009

Epistemic_statement

denotes

spa type 003 (ST225) was most frequent among MRSA followed by spa type 504 (previously rarely reported).

T1179

683010-683202

Epistemic_statement

denotes

A detailed risk assessment (multivariate analysis) revealed that previous MRSA history, chronic care, and presence of a skin wound/ulcer were significantly associated with MRSA carrier status.

T1180

683953-684078

Epistemic_statement

denotes

To date, however, little is known about the rate of MLVA variation and hence its usefulness for the tracing of transmissions.

T1181

685579-685593

Epistemic_statement

denotes

Interestingly.

T1182

685899-686141

Epistemic_statement

denotes

Our preliminary analyses describe the diversity of MLVA types in strains belonging to the same finetype obtained from different epidemiological settings; specifically, variation seems to increase according to presumed number of transmissions.

T1183

687464-687718

Epistemic_statement

denotes

Of note, in the non-ICU setting, extended-spectrum penicillins (J01CA), cephalosporins (J01DB-DE), carbapenems (J01DH) and quinolones (J01M) accounted (2009/2010) for 2.8%/2.4%, 39%/41.7%, 1.9%/2.2% and 11.7%/8% of the total antibiotic use, respectively.

T1184

688211-688363

Epistemic_statement

denotes

However, between the hospitals, we observed a broad range of antibiotic use both with respect to the density and the types of antimicrobial agents used.

T1185

688364-688535

Epistemic_statement

denotes

Together with regional data on bacterial antibiotic-resistance, this data can be used by the network hospitals for discussions aiming to improve local antibiotic policies.

T1186

689253-689388

Epistemic_statement

denotes

However for the control of vancomycin resistant enterococci (VRE) antibiotic stewardship with a focus on prudent use becomes necessary.

T1187

689389-689583

Epistemic_statement

denotes

The aim of this study was to determine risk factors in order to develop an algorithm for optimal empirical treatment in those patients who are at risk of E. faecium blood stream infection (BSI).

T1188

689946-690305

Epistemic_statement

denotes

Results: Significant associations of E. faecium BSI were found with age, hospital stay prior to blood culture, duration of hospitalization 1 year before admission, fever prior to blood culture, severity and duration of neutropenia, CRP (C-reactive protein) at time of blood culture withdrawal, colonization with E. faecium prior to blood culture and diarrhea.

T1189

690306-690396

Epistemic_statement

denotes

E. faecium BSIs were found associated with more severe disease and higher mortality rates.

T1190

690715-690853

Epistemic_statement

denotes

Conclusion: Empirical treatment should be considered in those hematologic patients who are at high risk for development of E. faecium BSI.

T1191

690854-691030

Epistemic_statement

denotes

Using a prognostic model for risk stratification as designed in this study prudent use of glycopeptides becomes possible and might be helpful controlling further spread of VRE.

T1192

691199-691281

Epistemic_statement

denotes

Molecular and phenotypical investigations of the clinical isolates were performed.

T1193

692451-692578

Epistemic_statement

denotes

ERIC-and REP-PCR analysis of the K. pneumoniae isolates of all patients showed an identical profile suggesting a clonal spread.

T1194

692721-692875

Epistemic_statement

denotes

Prior to the emergence of the Oxa-48 expressing E. coli a less resistant E. coli with an ESBL phenotype could be isolated several times from this patient.

T1195

693031-693130

Epistemic_statement

denotes

This strongly suggests the in vivo transfer of Oxa-48 from K. pneumoniae to E. coli in the patient.

T1196

693229-693369

Epistemic_statement

denotes

Epidemiological, molecular and phenotypical data suggest a horizontal interspecies transfer of Oxa-48 from K. pneumoniae to E. coli in vivo.

T1197

694349-694417

Epistemic_statement

denotes

126/737 (22%) patients could be included in the follow-up screening.

T1198

694418-694651

Epistemic_statement

denotes

Because 42/111 (37.8%) of the VRE-positive patients had been hospitalised for more than 72 hours before the first screening swabs, the distinction community vs. nosocomial acquisition could be made only for the remaining 69 patients.

T1199

694885-694967

Epistemic_statement

denotes

Interestingly, none of the VREpositive patients was previously known to carry VRE.

T1200

695568-695649

Epistemic_statement

denotes

Reasons for the high VRE prevalence may be the previous Vancomycin therapy (33%).

T1201

695709-695814

Epistemic_statement

denotes

Neither did colonisation predict consecutive infection, nor was the VRE status associated with mortality.

T1202

696038-696185

Epistemic_statement

denotes

Further studies are warranted to determine the role of the environmental contamination especially in a setting of moderate hand hygiene compliance.

T1203

697563-697702

Epistemic_statement

denotes

The proportion of infections with secondary bloodstream infections were significantly associated with the spa type t003 (OR 6.75; p=0.004).

T1204

697703-697801

Epistemic_statement

denotes

The spa type t032 was significantly less associated to secondary bloodstream infections (p=0.041).

T1205

697802-697940

Epistemic_statement

denotes

Conclusion: The molecular spa typing provided additional information to the epidemiological associations during routine MRSA surveillance.

T1206

698027-698084

Epistemic_statement

denotes

Further studies were needed to verify these observations.

T1207

698645-698781

Epistemic_statement

denotes

We evaluated the incidence of MRSA carriage at hospital admission and we investigated some risk factors associated to MRSA colonisation.

T1208

699617-699717

Epistemic_statement

denotes

However, only few data about its overall prevalence in certain geographical areas are yet available.

T1209

699904-700000

Epistemic_statement

denotes

In addition we checked for patient subgroups that may be at an increased risk for MRSA carriage.

T1210

700921-701126

Epistemic_statement

denotes

Within healthcare institutions, Methicillin-resistant Staphylococcus aureus (MRSA) can be transmitted from patient to patient or via healthcare workers' (HCW) hands, clothes, equipment and the environment.

T1211

701127-701289

Epistemic_statement

denotes

Few studies have evaluated the prevalence of MRSA colonization among HCW outside outbreak situations and the importance of staff as a real source of transmission.

T1212

702883-703007

Epistemic_statement

denotes

The therapy was successful after the first eradication cycle in 100 % of the cases and could be verified in follow-up swaps.

T1213

703727-703909

Epistemic_statement

denotes

Objective: Rates of VREF remain constant or are declining in Germany in recent years, but molecular analyses suggest a genotype switch from vanAtype to vanB-type among hospital VREF.

T1214

706112-706238

Epistemic_statement

denotes

Conclusion: Reliable detection of low level vancomycin expression in vanB-type VREF is a challenge in the clinical laboratory.

T1215

706239-706390

Epistemic_statement

denotes

Its delayed detection or unnoticed appearance may support further spread of vanB VREF and underestimate its true prevalence among the clinical setting.

T1216

706716-706815

Epistemic_statement

denotes

Multiresistant Pseudomonas (P.) aeruginosa is an increasing problem in health care facilities [1] .

T1217

706816-706934

Epistemic_statement

denotes

As one of the most important inhabitants of biofilms this Nonfermenter can consist in different reservoirs in clinics.

T1218

706935-707064

Epistemic_statement

denotes

The siphon traps of washing basins are colonized by different germs and may be an underestimated source of pathogen distribution.

T1219

707065-707279

Epistemic_statement

denotes

Long-term surveillance from 2007 to 2009 within a hemato-oncological setting with 24 isolation units for patients with allogenic stem cell transplantation revealed the association of emerging multiresistant P. spp.

T1220

707546-707642

Epistemic_statement

denotes

During this procedure it was very possible that the patients inhaled aerosols from siphon water.

T1221

707643-707764

Epistemic_statement

denotes

Responsible for this outbreak two strains could be detected by RAPD-PCR and specific P. aeruginosa microarray genotyping.

T1222

708151-708286

Epistemic_statement

denotes

The outbreak could be stopped by implementation of so called Hygiene siphons at the washing basin in all of the 24 isolation units (Fa.

T1223

708525-708714

Epistemic_statement

denotes

Even with maximum barrier infection control measures undertaken to avoid nosocomial infections hidden reservoirs like siphon traps of washing basins can be the source of pathogen outbreaks.

T1224

708715-708853

Epistemic_statement

denotes

The installation of Hygiene siphons in isolation units for high risk patients can help to reduce the distribution of multiresistant germs.

T1225

708854-709024

Epistemic_statement

denotes

Early molecular-epidemiological analysis is urgently needed to verify outbreak situations and is essential to implement specific and effective infection control measures.

T1226

709025-709138

Epistemic_statement

denotes

The gastrointestinal tract harbours a complex microbial ecosystem, engaged in continuous crosstalk with the host.

T1227

709139-709374

Epistemic_statement

denotes

The balanced relationship between intestinal epithelial cells (IECs) and gut microbes can be disturbed, resulting in the activation of the mucosal immune system which contributes to the development of inflammatory bowel diseases (IBD).

T1228

709528-709730

Epistemic_statement

denotes

As IBD may develop after defects of barrier function and based on our microarray data obtained with co-incubated IECs we focussed on proteins (ZO-2, PAR-3, PAR-6) of the apical junctional complex (AJC).

T1229

710103-710245

Epistemic_statement

denotes

Even after barrier disruption by EPEC, barrier function could be restored by incubation with probiotic EcN as monitored by an increase in TER.

T1230

710661-710813

Epistemic_statement

denotes

Further insight into the molecular targets of specific miRNAs might foster the development of new strategies for treatment of gastrointestinal diseases.

T1231

711127-711330

Epistemic_statement

denotes

Besides commensal and probiotic microorganisms there are also bacterial pathogens such as enteropathogenic E.coli that can cause diarrhea by exploitation of host cells and subversion of defense measures.

T1232

711331-711442

Epistemic_statement

denotes

How these pathogens interact with and subvert (immune) cells of the intestinal barrier is not fully understood.

T1233

712426-712500

Epistemic_statement

denotes

This is not observed with an EPEC mutant lacking the effector protein Tir.

T1234

712501-712629

Epistemic_statement

denotes

Interestingly, pedestal formation can be faintly detected also with mutants without functional type III secretion system (T3SS).

T1235

713246-713433

Epistemic_statement

denotes

The comparison of effects of pathogenic and probiotic bacteria on immune cells might reveal further insights into the molecular mechanisms that are impaired in gastrointestinal disorders.

T1236

714720-714843

Epistemic_statement

denotes

Surprisingly LP and MLN DCs of DSS mice expressed significantly higher amounts of TLR2 and TLR4 in comparison to mock mice.

T1237

714844-715011

Epistemic_statement

denotes

Increased appearance of CD103 + DCs and higher amounts of TLR2 and TLR4 are likely to be a counter regulation of the host in order to suppress developing inflammation.

T1238

715061-715231

Epistemic_statement

denotes

Introduction: The bacterial inventory of the human oral cavity is already fairly comprehensive and composed of about 800 different species many of which are uncultivated.

T1239

715232-715354

Epistemic_statement

denotes

However, the dynamics and variability of the oral microflora in relation to health or disease are still poorly understood.

T1240

715355-715544

Epistemic_statement

denotes

Our aim was to test the hypothesis, that the development of oral symptoms after multiple stressing of the immunosystem is related to the composition and diversity of the initial microflora.

T1241

716589-716796

Epistemic_statement

denotes

However, when comparing Group I and II an interaction signal of about 3% was consistently observed (under varying analytical parameters) while this was not the case when the two time points of sampling (i.e.

T1242

717084-717233

Epistemic_statement

denotes

Based on the Human Oral Microbiome Database (HOMD) distinct bacterial taxa could be elucidated as key-components explaining the observed differences.

T1243

717234-717545

Epistemic_statement

denotes

Discussion: The data indicate that there is a discernable relationship between susceptibility to clinical symptoms and the indigenous, pre-formed oral microbiota which means that the initial composition of the oral ecosystem determines whether or not symptoms develop upon exposure to various stress-parameters.

T1244

717821-717918

Epistemic_statement

denotes

But unlike all other I Bs, I B seems not only to be an inhibitor but more of a modulator of NF B.

T1245

718077-718236

Epistemic_statement

denotes

We hypothesize that I B at least partially contributes to DC semimaturation, as this process was shown to be dependent on presence of IL-6 and absence of TNF-.

T1246

718345-718433

Epistemic_statement

denotes

Due to this fact I B might play a crucial role in maintenance of intestinal homeostasis.

T1247

718434-718715

Epistemic_statement

denotes

To clarify the role of which might lead to the development of new strategies in treatment of inflammatory bowl diseases we analysed and compared in a first step the I B mRNA and protein expression in naïve, semimature and mature DC using quantitative PCR and western blot analysis.

T1248

718803-718936

Epistemic_statement

denotes

Future experiment will involve I B deficient mice, for generation of BMDC and the analysis of the impact of I B on acute DSS colitis.

T1249

719756-719858

Epistemic_statement

denotes

We could also show that all Symbioflor 2 E. coli clearly belong to the cluster of apathogenic E. coli.

T1250

719859-720047

Epistemic_statement

denotes

However, it is largely unknown which E. coli genotype is responsible for the products probiotic character and which genes and proteins are involved in the development of a probiotic trait.

T1251

720048-720184

Epistemic_statement

denotes

E. coli G3/10 has already attracted interest due to its ability of inducing defensin production in cell culture and in human volunteers.

T1252

720185-720457

Epistemic_statement

denotes

Using an in vitro adherence assay with human intestinal epithelial cells we could further show that E. coli G3/10 significantly decreases the adhesion of enteropathogenic E. coli strain E2348/69 (EPEC) to host cells, comparable to the probiotic strain E. coli Nissle 1917.

T1253

720574-720705

Epistemic_statement

denotes

The sequenced genomes together with in vitro data will help us to gain further insight into the probiotic behavior of Symbioflor 2.

T1254

722047-722259

Epistemic_statement

denotes

55 specific HaeIII T-RF signals could be assigned to various phylogenetic groups and we could show that microbial community structure was different between dental biofilms, saliva and interproximal dental plaque.

T1255

723020-723168

Epistemic_statement

denotes

We conclude that characteristic signatures of microbiota can be found in saliva, interproximal dental plaque and also during oral biofilm formation.

T1256

723169-723368

Epistemic_statement

denotes

Culture-independent analysis of microbiota may provide new insights into the microbial diversity in various communities which was shown here for different oral compartments and growing oral biofilms.

T1257

723555-723749

Epistemic_statement

denotes

However, when the balance of the normal flora is altered e. g. during antibiotic or hormonal therapy, C. albicans can cause painful cutaneous or subcutaneous infections including vulvovaginitis.

T1258

723972-724046

Epistemic_statement

denotes

However, the role of lactobacilli in candidal vulvovaginitis is not known.

T1259

724146-724300

Epistemic_statement

denotes

Therefore we analyzed how far lactobacilli may influence the yeast-hyphal transition has been described as a factor that facilitates the invasion process.

T1260

724606-724927

Epistemic_statement

denotes

We analyzed how far the different Lactobacillus strains influence the viability (XTT_reduction assay) of Candida as well as the expression of hyphae-specific genes (ALS3, HWP1, HYR1) Results: Only L. crispatus inhibited the growth of all Candida albicans isolates under study and diminished their viability significantly.

T1261

725235-725304

Epistemic_statement

denotes

Conclusion: From our results one may conclude that lactobacillus spp.

T1262

725305-725368

Epistemic_statement

denotes

may either favour or inhibit pathogenicity of Candida albicans.

T1263

725523-725644

Epistemic_statement

denotes

The gut of mammalians is colonised by a complex flora of microorganisms containing 500 -1000 different bacterial species.

T1264

725984-726022

Epistemic_statement

denotes

The mechanism however remains unclear.

T1265

726785-727031

Epistemic_statement

denotes

However, by the use of new culture-independent techniques unbiased semi-quantitative analysis of complex bacterial communities are now available which could help to better understand the role of microbiota in colonisation and pathogenicity of CF.

T1266

727542-727990

Epistemic_statement

denotes

This finding was supported by the culture-independent analysis of bacterial nucleic acid in respiratory samples using T-RFLP, however, we also found new aspects of respiratory infections by the culture-independent method with increasing rates of anaerobic bacteria in CF patients at older age which potentially contribute to clinical progression of CF lung disease; however, prospective clinical studies are required to confirm this new assumption.

T1267

728143-728406

Epistemic_statement

denotes

High relative abundance of Staphylococci (24%), Neisseria / Haemophilus (16%), Streptococci (9%), Bacteroidetes (6%) and Veillonella (5%) were found whereas the Pseudomonas species were detected with surprisingly low frequencies in samples (1%) of all age groups.

T1268

728459-728668

Epistemic_statement

denotes

T-RFLP) will fundamentally change the current view of polymicrobial lung infection in CF patients due to the unbiased detection of potentially new respiratory pathogens and due to the new quantitative aspects.

T1269

728669-728846

Epistemic_statement

denotes

We suppose that very soon culture-independent analysis of the respiratory microbiota could become a new diagnostic standard for optimized diagnostics and therapy of CF patients.

T1270

728939-729119

Epistemic_statement

denotes

Yet, opposite to the upper respiratory tract and the gut, the lower respiratory tract including lung has been considered free of foreign microorganisms, so it is vastly unexplored.

T1271

729120-729237

Epistemic_statement

denotes

To understand how lung micro-ecology affects host defense and infection, it is essential to identify lung commensals.

T1272

730248-730387

Epistemic_statement

denotes

Notably, we detected bacterial communities on alveolar epithelia by eubacteria specific FISH in the absence of inflammatory lung pathology.

T1273

730760-730955

Epistemic_statement

denotes

Ultimately, we expect that our lung isolates or major species by non-culture method can be introduced into mouse model experiment for lung commensalism as well as coinfection with lung pathogens.

T1274

731118-731304

Epistemic_statement

denotes

The salivary microbiome as an indicator of human-microbe coevolution Introduction: Human-associated bacteria hold great potential for shedding light on the history of our ancestors (i.e.

T1275

731463-731629

Epistemic_statement

denotes

We currently test the hypothesis that oral microbes may function as chronometer of human evolution thereby allowing a fine-scale differentiation of human populations.

T1276

732134-732314

Epistemic_statement

denotes

Results: The ITS region of F. nucleatum and the gdh of mitis-streptococci could be directly PCR-amplified from saliva DNA-extract using newly designed as well as published primers.

T1277

732637-732830

Epistemic_statement

denotes

Based on phylogenetic tree reconstruction most clusters consisted of sequence types which were representative for multiple countries, however, one country was typically dominating in a cluster.

T1278

732939-733072

Epistemic_statement

denotes

Discussion: Oral microbes found in saliva may exhibit a clonal structure and thus be representative for a distinct geographic region.

T1279

733073-733229

Epistemic_statement

denotes

Phylogenetic tools such as UniFrac are necessary to compute the distances within and between hosts in order to discern geographical and ethnic associations.

T1280

733230-733700

Epistemic_statement

denotes

Given that saliva is increasingly preferred in sampling humans as a source of DNA for epidemiologic and population genetic studies, the salivary microbiome may hold additional valuable information for providing new perspectives on unsolved human migration patterns -an issue of great social, anthropological, and medical importance Introduction: Clinical studies revealed that the probiotic mixture VSL#3 is protective in the context of inflammatory bowel disease (IBD).

T1281

734035-734170

Epistemic_statement

denotes

The aim of the present study was to identify the active probiotic structure triggering the loss of the proinflammatory chemokine IP-10.

T1282

736235-736790

Epistemic_statement

denotes

The identification of lactocepin as a probiotic structure could enable a more structure-based evaluation of probiotic bacteria for therapeutical interventions in the context of chronic inflammation PWV05 Flagellin and tcpC are essential factors of the protective effect of E. coli Nissle strain 1917 in DSS-induced colitis S. Menz* 1 , K. Gronbach 1 , P. Adam 2 , A. Wieser 3 , S. Schubert 3 , U. Dobrindt 4 , T. (EcN) is as effective as mesalazine in maintenance of remission in ulcerative colitis and shortens the duration of diarrhea in young children.

T1283

736791-736955

Epistemic_statement

denotes

We studied in a preclinical model of acute colitis whether EcN protects from disease and analysed the bacterial mechanism underlying the anti-inflammatory capacity.

T1284

737654-737805

Epistemic_statement

denotes

However a second bacterial factor tcpC also contributes to the protective effect of EcN as the tcpC mutant strain was not able to protect from disease.

T1285

737806-737885

Epistemic_statement

denotes

Administration of the double mutant fliC tcpC of EcN evidences this conclusion.

T1286

737988-738097

Epistemic_statement

denotes

However contribution of further bacterial factors to the anti-inflammatory effect of EcN can not be excluded.

T1287

738957-739100

Epistemic_statement

denotes

The observed discrepancy is most likely due to the lack of mucin on these cell lines, whereas mucus might still be present in the cryosections.

T1288

739651-739805

Epistemic_statement

denotes

In contrast, the E. coli strain CFT073 harboring and expressing an identical fliC gene adhered as inefficient to mucin2 as EcN fliC for unknown reason(s).

T1289

739931-740031

Epistemic_statement

denotes

This is in contrast to the general assumption, that E. coli are peritrichously flagellated bacteria.

T1290

740180-740284

Epistemic_statement

denotes

Therefore, this organelle might be of importance for efficient, transient colonization of the human gut.

T1291

740678-740737

Epistemic_statement

denotes

However, the underlying molecular networks are ill defined.

T1292

741277-741512

Epistemic_statement

denotes

While bacteria control the generation of B cell-containing isolated lymphoid follicles (ILF) from B cell-free cryptopatches, it is unknown whether the development of cryptopatches is programmed or also instructed by environmental cues.

T1293

741513-741756

Epistemic_statement

denotes

The family of Per-Arnt-Sim (PAS) domain-containing proteins is conserved throughout all eukaryotic species and it is believed that this group of proteins has evolved to control adaptation of multicellular organisms to environmental challenges.

T1294

741999-742142

Epistemic_statement

denotes

Although the role of the AhR in the response to environmental toxins is appreciated, its role in the mucosal immune system is not well defined.

T1295

742143-742281

Epistemic_statement

denotes

We addressed the role of the AhR for development and function of ROR t + ILC by generating mice lacking the AhR in ROR t + ILC (Ahr LTi ).

T1296

742282-742345

Epistemic_statement

denotes

Interestingly, Ahr LTi lacked genesis of cryptopatches and ILF.

T1297

743509-743640

Epistemic_statement

denotes

The aim of our study was to investigate whether proteases produced by commensal gut bacteria contribute to the pathogenesis of IBD.

T1298

744535-744731

Epistemic_statement

denotes

Furthermore, using LC-MS/MS analysis, we could indentify cleavage sites for GelE in the sequence of recombinant murine E-Cadherin suggesting the possibility for a direct GelE-mediated degradation.

T1299

744961-745054

Epistemic_statement

denotes

The loss of barrier integrity was associated with reduced levels of extracellular E-Cadherin.

T1300

745236-745437

Epistemic_statement

denotes

We could show specificity for the GelE-mediated loss of barrier function by using an E. faecalis lipoprotein as unrelated control and the broad spectrum MMP inhibitor Marimastat to block GelE activity.

T1301

745746-745801

Epistemic_statement

denotes

Dendritic cells (DCs) can provide different phenotypes.

T1302

745802-745892

Epistemic_statement

denotes

They can display an immature DC (iDC) phenotype or an activated mature DC (mDC) phenotype.

T1303

745893-745967

Epistemic_statement

denotes

Recently a third phenotype has been discovered, termed semimature (smDCs).

T1304

746611-746811

Epistemic_statement

denotes

Therefore we suggest that semi-maturation plays an important role in maintaining the intestinal homeostasis and that regulation of Cathepsin S could be a potential target for the treatment of colitis.

T1305

746826-746971

Epistemic_statement

denotes

An average number of 4202 sequences were obtained per tissue sample (mean length, 234 bp), and 98.5% of sequences could be classified into phyla.

T1306

747620-747830

Epistemic_statement

denotes

These differences were associated with highly significant differences of microbiota composition, which are likely responsible for attenuating responses to H. hepaticus in mice housed at one of the institutions.

T1307

748762-748860

Epistemic_statement

denotes

Thus they have not been the target for many commercial companies manufacturing these technologies.

T1308

748861-749007

Epistemic_statement

denotes

There is however a need for efficiency and improved quality provided by standardised procedures that are optimally furnished by automated systems.

T1309

749008-749391

Epistemic_statement

denotes

Methods: A university diagnostic laboratory providing a service to approximately 1800 in-patient beds, most of which (1200) are in a tertiary care / university setting and the remainder in a satellite teaching hospital also providing tertiary care, underwent a trial of an automated inoculation apparatus, with a view to further automatisation and integration of advanced technology.

T1310

750900-751098

Epistemic_statement

denotes

In this setting automatisation can be of great benefit by freeing technical staff for more tasks more appropriate to their training and also to the demands of a tertiary care / reference laboratory.

T1311

751240-751414

Epistemic_statement

denotes

As the spirochete resists conventional cultivation and to overcome test specific limitations, laboratory diagnosis is based on a stepwise approach using immunological assays.

T1312

751415-751590

Epistemic_statement

denotes

However, independent clinical evaluation of such tests is not mandatory within the EU and currently, a large number of assays of variable analytical quality are on the market.

T1313

752963-753252

Epistemic_statement

denotes

In this study we confirm previous investigations that, although positive trends are obvious, the sensitivity and specificity of currently applied assays for syphilis diagnostics can still vary substantially, depending on the stage of disease, the type of test and the kind of manufacturer.

T1314

753253-753508

Epistemic_statement

denotes

Our results demonstrate that ongoing external quality control of routine diagnostic laboratories and in depth clinical evaluation of diagnostic assays is clearly needed to monitor test quality and to ensure a high level of quality in syphilis diagnostics.

T1315

753509-753731

Epistemic_statement

denotes

External quality control of immunodiagnostics in rare and fastidious pathogens (bordetella, mycoplasma, coxiella, campylobacter, and yersinia): a metaanalysis of proficiency testing trials K.-P. Hunfeld* 1 , I. Müller 1 1

T1316

753732-753926

Epistemic_statement

denotes

Introduction: There is a long tradition in the participation of medical laboratories in external quality control of well established parameters and diagnostic procedures in medical microbiology.

T1317

753927-754029

Epistemic_statement

denotes

This tradition is now additionally enforced by the new guidelines of the German chamber of physicians.

T1318

754030-754155

Epistemic_statement

denotes

Evaluations of proficiency testing trials of indirect detection methods for rare and fastidious pathogens however are sparse.

T1319

754156-754346

Epistemic_statement

denotes

Most importantly the participation in such surveys is not mandatory in Germany although there is a lack of test standardization and very few data are available on the quality of such assays.

T1320

756119-756410

Epistemic_statement

denotes

Discussion: Although, proficiency testing trials cannot fully substitute clinical evaluations of immunodiagnostic tests, the results of our metaanalysis demonstrate a very variable degree of standardization and assay quality in the serodiagnostics of rare and fastidious bacterial pathogens.

T1321

756411-756771

Epistemic_statement

denotes

Most importantly, our observations provide interesting insights into the comparability of different assay systems the interpretation of quantitative and semi quantitative test results and the correct clinical interpretation of the serological findings pointing to limitations of these diagnostic procedures in the routine diagnostic microbiological laboratory.

T1322

756883-756991

Epistemic_statement

denotes

It has been shown an association between nasal colonization of S. aureus and infection with the same strain.

T1323

756992-757114

Epistemic_statement

denotes

Of particular concern is a worldwide increase in the number of infections caused by methicllin-resistant S. aureus (MRSA).

T1324

758745-759090

Epistemic_statement

denotes

We observed association the more predominant MRSA clone the more virulence genes were detected: t003 -15 genes (sea, sed, seg, sei, sej, selm, seln, selo, ser, selu, lukD, lukE, sak, chp, scn); t032 -12 genes (sec, sed, seg, sei, sel, selm, seln, selo, selu, sak, chp, scn); t004 -10 genes (sed, seg, sei, selm, seln, selo, selu, sak, chp, scn).

T1325

759091-759305

Epistemic_statement

denotes

Although, most of the la-MRSA carry no tested virulence factors, some la-MRSA harbour important virulence factors which shows the genomic plasticity of this MRSA subtype and possible adaptive changes in the future.

T1326

759614-759797

Epistemic_statement

denotes

Originally associated with consumption of raw milk and dairy products or contact to cattle, C. ulcerans has increasingly been isolated from domestic animals such as pet dogs and cats.

T1327

759929-760089

Epistemic_statement

denotes

Here we report the first case of proven transmission of a toxigenic C. ulcerans strain between a pet cat and a human causing pharyngeal diphtheria-like illness.

T1328

760231-760514

Epistemic_statement

denotes

Objectives: Human infections due to Corynebacterium diphtheriae and the zoonotic germs C. ulcerans and C. pseudotuberculosis are rare but potentially life-threatening events requiring specific antibiotic treatment, and in cases suspicious for diphtheria the prompt antitoxin therapy.

T1329

760731-760973

Epistemic_statement

denotes

Benzyl penicillin and erythromycin are still recommended for specific antibiotic treatment, to eradicate the pathogen in patients and to prevent infection among contacts, although only very few antimicrobial susceptibility data are available.

T1330

761627-761819

Epistemic_statement

denotes

Results: Benzyl penicillin, erythromycin and ciprofloxacin seem to be highly active substances in all three Corynebacterium species (susceptibility rates of 98.1, 98.1 and 96.2% respectively).

T1331

762130-762300

Epistemic_statement

denotes

Conclusion: Our data emphasize the need for an accurate species identification of potentially toxigenic corynebacteria and underscore the necessity of antibiotic testing.

T1332

762301-762499

Epistemic_statement

denotes

Although clindamycin is not a first-line drug in diphtheria therapy, it is favoured for the treatment of wound infections, but due to our results C. ulcerans is not surely covered by this substance.

T1333

762500-762642

Epistemic_statement

denotes

Benzyl penicillin and erythromycin can be still recommended for specific antibiotic treatment in Germany, but antibiotic resistance may occur.

T1334

763644-763734

Epistemic_statement

denotes

Following our phylogenetic analyses, this isolate can be identified as Helicobacter felis.

T1335

763948-764060

Epistemic_statement

denotes

Infections in humans have been reported, but culture is difficult due to the fastidious nature of this organism.

T1336

764400-764503

Epistemic_statement

denotes

Furthermore, culture of fastidious non-H. pylori helicobacters using our standard protocol is possible.

T1337

764645-765001

Epistemic_statement

denotes

Stüger 2 , E. Glocker 1 , M. Kist 1 1 Institute of Medical Microbiology and Hygiene, National Reference Centre for Helicobacter pylori, Freiburg, Deutschland 2 Austrian Agency for Health and Food Safety, Graz, Oesterreich Introduction: Metronidazole is part of the Italian triple therapy, which is a recommended first line scheme for H. pylori eradication.

T1338

765158-765320

Epistemic_statement

denotes

However, phenotypic susceptibility testing is currently not approved by the FDA due to "variance in test results, lack of reproducibility and clinical relevance".

T1339

765486-765653

Epistemic_statement

denotes

Therefore, the aim of our study is to evaluate factors that influence the precision and reproducibility of metronidazole susceptibility testing using the Etest method.

T1340

766171-766331

Epistemic_statement

denotes

Results: The minimal inhibitory concentrations (MIC) detected on Mueller-Hinton and Isosensitest agar after 48h and 72h of incubation showed a high correlation.

T1341

766688-766862

Epistemic_statement

denotes

Discussion: There is a small but systematic influence of culture media and incubation period on metronidazole testing using the Etest method, but correlation of MICs is high.

T1342

766863-766919

Epistemic_statement

denotes

To evaluate the reproducibility further data are needed.

T1343

766920-767464

Epistemic_statement

denotes

J. Kolb* 1 , D. Hillemann 1 , J. Reetz 2 , S. Rüsch-Gerdes 1 , E. Richter 1 1 Forschungszentrum Borstel, Nationales Referenzzentrum für Mykobakterien, Borstel, Deutschland 2 Bundesinstitut für Risikobewertung, Berlin, Deutschland Introduction: One of the most frequent isolated species within nontuberculous mycobacteria is M. avium, which is ubiquitously found in the environment and has been shown to be responsible for a variety of human diseases, mainly in immunocomprised patients, but also in patients with no obvious immune deficiencies.

T1344

767617-767654

Epistemic_statement

denotes

Routes of infection are rarely known.

T1345

767817-767939

Epistemic_statement

denotes

Therefore, the aim of our study was to assess the applicability of MLST and MIRU-VNTR for distinguishing M. avium strains.

T1346

768674-768775

Epistemic_statement

denotes

Various single nucleotide polymorphisms could be detected by MLST analysis in the genes investigated.

T1347

768776-768894

Epistemic_statement

denotes

Differences in the genes concerning their variability were used to decide the applicability for future investigations.

T1348

768972-769046

Epistemic_statement

denotes

Discussion: By molecular methods subspecies of M. avium can be identified.

T1349

769047-769180

Epistemic_statement

denotes

MLST enables typing of strains that in future may be used for example for analysis of transmission or reactivation vs. new infection.

T1350

771035-771124

Epistemic_statement

denotes

However, the serotype distribution among these isolates has changed considerably as well.

T1351

771295-771418

Epistemic_statement

denotes

The observed reduction of IPD cases with vaccine serotypes in older children and adults indicates a herd protection effect.

T1352

771710-771920

Epistemic_statement

denotes

Establishment of a red deer DNA banc as source for future studies on emerging zoonotic and vector borne pathogens C. Klier* 1 , J. Brenauer 1 , B. Fleischer 2 , E. Gerstmair 1 , M. Niedrig 3 , Y. Schulze 3 , A.

T1353

771921-772398

Epistemic_statement

denotes

Sing 1 , V. Fingerle 1 1 LGL Bayern, NRZ Borrelien,, Oberschleißheim, Deutschland 2 Bernhard-Nocht-Institut , Nationales Referenzzentrum für tropische Infektionserreger, Hamburg, Deutschland 3 Robert Koch Institut, Konsiliarlabor für FSME , Berlin, Deutschland Background: Ongoing global warming is thought to cause environmental changes which could foster the emergence and re-emergence of zoonotic as well as vectorborne infectious diseases affecting human and animal health.

T1354

772515-772712

Epistemic_statement

denotes

To date there is little data available on the prevalence of zoonotic and vector borne pathogens such as Anaplasma phagocytophilum, Francisella tularensis, Babesia spp, Rickettsia spp, or TBE-Virus.

T1355

772713-772928

Epistemic_statement

denotes

Data obtained in seroprevalence studies indicate that wild animals are susceptible to several zoonotic and vector borne pathogens, however do not provide informations to which extend wild animals serve as reservoir.

T1356

772929-773136

Epistemic_statement

denotes

In this study we aim at 1) establishing a DNA banc from well defined material from red deer and 2) to perform first investigations on the prevalence of zoonotic and vector borne pathogens in these materials.

T1357

773137-773303

Epistemic_statement

denotes

Standardized collected and stored DNA-samples may serve as a material collection for longitudinal studies on endemic and emerging zoonotic and vector borne pathogens.

T1358

774173-774248

Epistemic_statement

denotes

Further pathogenscreening actually is on the way and data will be provided.

T1359

774373-774560

Epistemic_statement

denotes

Conclusion: The detection of A. phagocytophilum DNA in the screened samples indicates that lymph nodes from red deer is suitable for screening purposes with respect to A. phagocytophilum.

T1360

774561-774670

Epistemic_statement

denotes

The absence of F. tularensis DNA in lymph nodes however does not conclusively rule out red deer as reservoir.

T1361

774671-774809

Epistemic_statement

denotes

Due to the high mobility and broad distribution of red deer, it might serve as a sentinel for emerging zoonotic and vectorborne pathogens.

T1362

774810-774910

Epistemic_statement

denotes

The presented DNA banc is an important prerequisite for future investigations on emerging pathogens.

T1363

774994-775232

Epistemic_statement

denotes

Infection with Borrelia can result in clinical manifestations of the skin (Erythema migrans, Borrelia lymphocytoma, Acrodermatitis chronica atrophicans), nervous system (neuroborreliosis), joints (Lyme Arthritis) or heart (Lyme Carditis).

T1364

775233-775310

Epistemic_statement

denotes

Currently concise data on the incidences of LB in European countries is rare.

T1365

775674-775830

Epistemic_statement

denotes

Reporting regimens are very heterogenous among European countries and there is little information on the reliability of the employed reporting systems (e.g.

T1366

776671-776781

Epistemic_statement

denotes

Longitudinal data on the incidence of LB in Europe indicate that some countries observe a clear increase, e.g.

T1367

777284-777387

Epistemic_statement

denotes

For the purpose of comparable data, well designed sentinels or prospective studies are urgently needed.

T1368

777556-777726

Epistemic_statement

denotes

In case of infection with B. spielmanii or B. valaisiana the melting curve analysis could not differentiate between the two species because of overlapping melting curves.

T1369

777920-778048

Epistemic_statement

denotes

Preliminary results suggest that there is a low risk to develop Lyme borreliosis after a Borrelia-infected tick bite in Romania.

T1370

778581-778706

Epistemic_statement

denotes

Quantitative results were converted into IU/ml wherever possible using the suggestions from the producers of diagnostic kits.

T1371

779527-779704

Epistemic_statement

denotes

Conclusions: Many laboratories used methods that are not recommended by the EU reference laboratories and report results that cannot be related to the WHO reference preparation.

T1372

779705-780079

Epistemic_statement

denotes

Retrospective performance of HRM-PCR to discover two outbreaks of listeriosis in Austria, 2008 -2010 Introduction: For public health laboratories in charge of listeriosis surveillance, high-resolution melting PCR (HRM-PCR) analysis is a promising new technique to get by with low specificity of serotyping and various disadvantages of pulsed field gelelectrophoresis (PFGE).

T1373

781872-781998

Epistemic_statement

denotes

Conclusions: HRM-PCR analysis appears to be a sensitive, fast and inexpensive screening method to discover possible outbreaks.

T1374

782540-782630

Epistemic_statement

denotes

Although particular clonal lineages were associated with particular geographic areas (e.g.

T1375

783648-783714

Epistemic_statement

denotes

However, a considerable portion of them was lacking arcA and mphB.

T1376

783863-783980

Epistemic_statement

denotes

Although finding of the same rudimentary inverted repeat in the fosB vicinity and of sek and set suggest relatedness.

T1377

784104-784308

Epistemic_statement

denotes

Furthermore CA-MRSA clones which belonged to ST1, ST5, ST22, ST152 The capsule-specific synthesis (cap) regions II of Haemophilus influenzae serotypes c and d (Hic and Hid) were unknown before this study.

T1378

785159-785217

Epistemic_statement

denotes

Ccs2 seems to be a member of glycosyltransferase family 2.

T1379

785811-785980

Epistemic_statement

denotes

Their putative role in the conversion of -D-GlcNAc to -D-ManANAc corresponds to the repetitive disaccharide units -D-GlcNAc and -D-ManANAc of the capsule polysaccharide.

T1380

786104-786251

Epistemic_statement

denotes

as well as to more distant genera including N. meningitidis suggest horizontal gene transfer during capsule evolution across the bacterial classes.

T1381

787203-788067

Epistemic_statement

denotes

Within the year 2010, about 6000 bacterial samples from human disease cases were analyzed and among others the following interesting observations with respect to typing of the strains were made: 1) Reduction in occurrence of the formerly leading Salmonella enterica serovar Enteritidis 2) Increase in occurrence of monophasic Salmonella enterica serovar Typhimurium strains 3) Increased observation of Salmonella infections in children caused by rare serotypes and the link to reptile presence in households 4) Virulence gene fingerprinting of disease-associated intestinal E. coli and characterization of intermediate E. coli strains which contain virulence genes or plasmids from different pathotypes 5) Work on outbreaks or family-associated cases due to Salmonella (75), E. coli (31, EHEC and EPEC), Campylobacter (10), Shigella sonnei (2) , and Listeria (2) .

T1382

789140-789374

Epistemic_statement

denotes

Even though phenotypic susceptibility testing, as standardised by the NRC, has been shown to be reliable and reproducible, it may fail due to extra-long transport times, incorrect handling of gastric tissue samples and contaminations.

T1383

789754-789978

Epistemic_statement

denotes

Since 2006, the NRC has been offering gastroenterologists a unique service: on request, they are sent individual treatment recommendations based on the antimicrobial resistance patterns of their patients' H. pylori isolates.

T1384

789979-790180

Epistemic_statement

denotes

Data on the outcome of the so far more than 1500 therapy recommendations will be analysed and will provide precious data to work out optimised treatment recommendations for difficult-to-treat patients.

T1385

790181-790582

Epistemic_statement

denotes

10 years after being founded, the NRC for H. pylori established itself as an indispensable institution needed to (i) improve the diagnosis of H. pylori related infections; (ii) to control the development of antimicrobial resistance in H. pylori; (iii) to standardise antimicrobial susceptibility testing procedures; and (iv) to give treatment recommendations in difficultto-treat H. pylori infections.

T1386

790583-791049

Epistemic_statement

denotes

Characterization of livestock-associated methicillin-resistant Staphylococcus aureus (MRSA) using multiple-locus variable number of tandem repeats analysis (MLVA) K. Brandt* 1 , A. Mellmann 1 , C. Jenke 1 , R. Köck 1 1 University Hospital Münster, Institute for Hygiene, Münster, Deutschland Staphylococcus aureus is an important human pathogen and the emergence of methicillin-resistant S. aureus (MRSA) has become a major concern especially in healthcare settings.

T1387

791452-791670

Epistemic_statement

denotes

However, studies have shown that zoonotic MRSA-isolates from livestock mainly belong to the MLST clonal complex 398 and are mostly associated with a limited subset of spa types (predominantly with t011, t108 and t034).

T1388

791671-791876

Epistemic_statement

denotes

To assess the range of genetic diversity among these MRSA isolates, we investigate in whether multiple-locus variable number of tandem repeats analysis (MLVA) provides a greater resolution than spa-typing.

T1389

792061-792253

Epistemic_statement

denotes

We aim to investigate the diversity of livestock-associated MRSA isolates derived between 2005 and 2010 from more than 50 pig stables comprising locations in various federal states of Germany.

T1390

792254-792414

Epistemic_statement

denotes

First results of MLVA show that by spa-typing indistinguishable strains of different geographic regions can be clustered into at least two different MLVA-types.

T1391

792415-792544

Epistemic_statement

denotes

MLVA discriminated isolates associated with spa-type t011 from two different pig farms assigning them to MLVA-types 398 and 2215.

T1392

792545-792685

Epistemic_statement

denotes

Yet, the MLVA profiles identified so far differ in only one locus which supports the theory of a clonal origin of livestock-associated MRSA.

T1393

792686-792840

Epistemic_statement

denotes

MLVA typing of zoonotic MRSA might therefore contribute to a better understanding of its genetic diversity against a geographical and temporal background.

T1394

792841-793006

Epistemic_statement

denotes

Our findings will finally add valuable information to investigate the transmission dynamics of a zoonotic pathogen that has only recently overcome a species barrier.

T1395

793158-793531

Epistemic_statement

denotes

Schmidt 1 , G. Schares 2 , P. Maksimov 2 , W. Däubener 1 1 Institut für Medizinische Mikrobiologie und Krankenhaushygiene, Düsseldorf, Deutschland 2 Institut für Epidemiologie, Friedrich Löffler Institut, Wusterhausen, Deutschland Neospora caninum (N. caninum) is an obligate intracellular apicomplexan parasite which is very close related to Toxoplasma gondii (T. gondii).

T1396

794035-794211

Epistemic_statement

denotes

After production of a N. caninum specific anti-GRA9 antiserum against the recombinant protein it could be shown by Western Blot that the NcGRA9 gene encodes a 40,2 kDa protein.

T1397

794500-794640

Epistemic_statement

denotes

Furthermore, we could show that after invasion of the parasites into the host cell NcGRA9 is secreted into the parasitophorous vacuole (PV).

T1398

794703-794944

Epistemic_statement

denotes

In sum, we could verify in this study that NcGRA9 and TgGRA9 are structurally similar, show immunological cross reactivity and are similar distributed within the respective parasites which indicate a close relationship between both proteins.

T1399

795207-795324

Epistemic_statement

denotes

In host cells the parasite develops within a parasitophorous vacuole (PV), which causes handicaps in nutrient supply.

T1400

795749-795949

Epistemic_statement

denotes

Recent coimmunoprecipitation data indicate that GRA9 is a major interaction partner of GRA7 and GRA3 which both were found to be important in nutrient transport between the host cell and the parasite.

T1401

796167-796283

Epistemic_statement

denotes

Results indicate that the C-terminus of GRA9 is essential and sufficient for the correct GRA9 secretion into the PV.

T1402

796284-796416

Epistemic_statement

denotes

GRA9-proteins lacking the last one hundred amino acids, including two hydrophobic domains show an alteration in secretion behaviour.

T1403

796417-796555

Epistemic_statement

denotes

The C-terminal truncated GRA9-protein was found exclusively within the cytoplasm of the parasites and could not enter the lumen of the PV.

T1404

796556-796866

Epistemic_statement

denotes

Advances in the biomolecular interaction analysis of immunoglobulin-binding protein EibG from Shiga toxinproducing Escherichia coli Shiga toxin-producing Escherichia coli (STEC) can cause diarrhea and the hemolytic uremic syndrome (HUS) in humans and belong therefore to a group of pathogens of major interest.

T1405

797097-797236

Epistemic_statement

denotes

Additionally to the potential evasion of host immune response, EibG is involved in bacterial adherence to host intestinal epithelial cells.

T1406

797670-797865

Epistemic_statement

denotes

The possible functional role of glycosylation of IgG, harboring N-glycans in the CH2 domain of the Fc fragment, in EibG affinity was investigated with native and enzymatically deglycosylated IgG.

T1407

798059-798325

Epistemic_statement

denotes

Next EibG affinity to IgG subtypes of different vertebrate species was determined by ELISA under variable conditions aimed at identification of Igs with high binding affinity to EibG that may facilitate efficient isolation and purification of EibG from cell lysates.

T1408

798326-798506

Epistemic_statement

denotes

Pending determination of the amino acid sequences of EibG variants will be performed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS).

T1409

798507-798665

Epistemic_statement

denotes

Thus, peptide mapping and comparison to sequences of other Eib-proteins should help to unravel the molecular mechanisms of IgG-binding and cellular adherence.

T1410

798666-798897

Epistemic_statement

denotes

Furthermore, in search of the cellular receptors of epithelial cells, the potential affinity of EibG to glycosphingolipids of different biological origin will be explored by thin-layer chromatography (TLC) overlay assay techniques.

T1411

799191-799261

Epistemic_statement

denotes

Recently complement has also been shown to be involved in typical HUS.

T1412

799262-799499

Epistemic_statement

denotes

In this study, mostly weakly significant associations with homozygosities of complement allotype C7 M and inversely with factor H 402H were found, suggesting that 402Y and C7 M allotypes predispose to (typical) hemolytic uremic syndrome.

T1413

799864-800079

Epistemic_statement

denotes

Clinical signs are extremely variable, ranging from asymptomatic to chronic symptoms including severe diarrhoea and abdominal pain, and the contributing factors and mechanisms of pathophysiology are largely unknown.

T1414

800080-800317

Epistemic_statement

denotes

The zoonosis potential of distinct Giardia intestinalis genotypes has been highlighted, however, definition of specific parasite virulence factors and host risk factors has been hampered by the lack of functional epidemiological studies.

T1415

800318-800652

Epistemic_statement

denotes

The aim of this project is to built-up a unique database-linked biobank collection of Giardia intestinalis from human clinical cases and isolates from the field or from domestic animals and thus connecting epidemiological data and molecular characteristics with in-vitro functional test using the respective parasite isolate cultures.

T1416

800653-800751

Epistemic_statement

denotes

Subsequently, we will exploit the data and clonal parasite collection for functional studies, e.g.

T1417

800752-800857

Epistemic_statement

denotes

to correlate genotype-specific variations in potential virulence factors with functional characteristics.

T1418

801201-801448

Epistemic_statement

denotes

First genotyping results of cloned parasites at the glutamate dehydrogenase gene locus indicate a successful establishment of assemblage B sub-cultures, which are more difficult to isolate than assemblage A due to slower growth behaviour in vitro.

T1419

803789-803999

Epistemic_statement

denotes

Hence the here presented tool assist users strongly during their studies on novel aspects and hypotheses in their research field when providing the complete accessible knowledge in a fast and structured manner.

T1420

804000-804050

Epistemic_statement

denotes

Now, knowledge is there where knowledge should be.

T1421

805429-805649

Epistemic_statement

denotes

If querying annotated genomes, the user may choose various output file formats such as a list of orthologous core ORFs, the sequence of the core ORFs for a reference strain, and/or these core ORFs sequences concatenated.

T1422

806139-806311

Epistemic_statement

denotes

All non-core ORFs are reported to the User in categorized files (e.g., multi-copy ORFs, alternative start and/or stop codons, gaps in alignments, <95% sequence similarity).

T1423

806312-806481

Epistemic_statement

denotes

Conclusions: The Microbial Core Genome analysis tool, MCGenome, can be used to comparatively analyze multiple annotated genomes or interrogate a single un-annotated one.

T1424

807021-807114

Epistemic_statement

denotes

The spargana invade the brain, eye, viscera, and the subcutis, and can cause serious illness.

T1425

807115-807283

Epistemic_statement

denotes

A rare and complicated form, disseminated proliferative sparganosis, is caused by a branching, maldifferentiated plerocercoid provisionally termed Sparganum proliferum.

T1426

808534-808678

Epistemic_statement

denotes

Conclusion: Spirometra erinaceieuropaei has a cosmopolitan distribution, but most human cases occur in Asia possibly due to local eating habits.

T1427

808679-808891

Epistemic_statement

denotes

PCR analysis unambiguously identified the species responsible for the patient's disease and thus excluded the more pathogenic Sparganum proliferum, a larval cestode for which the adult strobilar stage is unknown.

T1428

809822-810009

Epistemic_statement

denotes

Conclusion: Human doctors as well as veterinarians should be prepared to come across cases of Dirofilariasis in Romania, as well as in other European countries regarded nonendemic so far.

T1429

810783-811018

Epistemic_statement

denotes

The strains carried four different eae alleles ( , , and a) which were associated with particular serotypes/fliC types: strains O157:H -[fliCH7] carried eae-g, O157:H16/H -[fliCH16] and O157:H34 eae-, O157:H39 eae-, and O157:H45 eae-a.

T1430

811427-811631

Epistemic_statement

denotes

Phylogenetic analysis of the 31 Stx-negative SF O157 strains using multilocus sequence typing demonstrated five different sequence types (STs 11, 10, 752, 1041, 593) and O157:H16 were associated with HUS.

T1431

811632-811838

Epistemic_statement

denotes

Our data demonstrate that the group of E. coli O157 pathogenic for humans is broader than previously thought and includes, besides classical nSF STEC O157:H7 also SF E. coli O157 of several other serotypes.

T1432

812427-812598

Epistemic_statement

denotes

In contrast to the wellstudied EHEC O157:H7, only little is known about the genome content and genome plasticity (e. g. loss of Stx-encoding genes [stx]) of this serotype.

T1433

813688-813785

Epistemic_statement

denotes

Interestingly, the SNP in rpoS (position 443, TAG to TGG) resolved a stopcodon to an intact gene.

T1434

813786-813929

Epistemic_statement

denotes

RpoS plays a crucial role in survival against stress and controls a large regulon, among them KatE (catalase HPII), which is dependent on RpoS.

T1435

814054-814168

Epistemic_statement

denotes

MalT, the transcriptional activator of maltose-regulon genes, may be also involved in protection against stresses.

T1436

814169-814339

Epistemic_statement

denotes

In contrast, the change in MreB, which is involved in cell division, chromosome segregation, and is responsible for the typical rod shape of cells, is not understood yet.

T1437

814340-814561

Epistemic_statement

denotes

Interestingly, synonymous SNPs, which usually represent the molecular clock and the normal mutation rate within a chromosome, were not detected indicating that external factors were responsible for the pathogens´ changes.

T1438

814738-814838

Epistemic_statement

denotes

Further studies will focus on the impact of the phenotypic changes to the host-pathogen interaction.

T1439

815029-815157

Epistemic_statement

denotes

D. repens can accidentally infect humans, which usually results in a subcutaneous nodule containing a single infertile parasite.

T1440

815767-815903

Epistemic_statement

denotes

In the recent years we diagnosed more cases of human D. repens infections than ever before, suggesting an increasing rate of infections.

T1441

815904-816026

Epistemic_statement

denotes

It has been postulated that climate warming will lead to spread of D. repens infections even to regions north of the Alps.

T1442

816273-816434

Epistemic_statement

denotes

Conclusion: The number of D. repens infections seems to be increasing and doctors should be prepared to diagnose and treat corresponding infections in travelers.

T1443

816955-817096

Epistemic_statement

denotes

However, PrP C is composed of several overlapping types in brain protein complexes but little is known about the composition of the subtypes.

T1444

817913-818095

Epistemic_statement

denotes

Our findings demonstrate that heterogenous PrP C phenotypes overlapping in brains may be separated regarding their solubility characteristics and convey distinct solubility subtypes.

T1445

818096-818347

Epistemic_statement

denotes

Protein differentiation by solubility experiments can therefore facilitate the separation of PrP C types, can provide detailed information on protein composition and can offer new prospects for transformation efficiency to PrP Sc by conversion assays.

T1446

819433-819584

Epistemic_statement

denotes

Transcriptomic and proteomic characterisation of these strains suggested changes in expression of flagellar genes, which may explain the AAG phenotype.

T1447

819752-819927

Epistemic_statement

denotes

All mutants colonized the mouse intestine to similar levels as the wildtype strain, but differed in their potential to induce diarrhea and inflammatory responses in the colon.

T1448

820094-820351

Epistemic_statement

denotes

Conclusion/Significance: Although there are subtle phenotypes associated with these putative RNA-binding proteins, there is currently no proof that these proteins function as general RNA-chaperones, as the predicted pleiotropic phenotypes were not observed.

T1449

820500-820738

Epistemic_statement

denotes

Adherent-Invasive Escherichia coli (AIEC), which have been associated with Crohn's disease, show traits similar to human and animal extraintestinal pathogenic E. coli (ExPEC) regarding their phylogenetic origin and virulence gene profile.

T1450

820739-820988

Epistemic_statement

denotes

However, previous studies have shown that human ExPEC strains rarely share the AIEC phenotype, whereas only limited data are available on the AIEC-like phenotype properties of animal E. coli strains, both from extraintestinal and intestinal sources.

T1451

820989-821271

Epistemic_statement

denotes

We therefore analyzed the AIEC phenotype of 79 ExPEC strains from birds, cats, dogs, and swine, which were selected with respect to multi locus sequence types (STs) that had previously been linked with AIEC strains from patients with Crohn's disease, including ST131, ST73 and ST10.

T1452

821826-821978

Epistemic_statement

denotes

Interestingly, none of the STC73 ExPEC strains showed this phenotype, whereas 72.4% of STC73 strains from enteritis were confirmed as AIEC-like strains.

T1453

821979-822234

Epistemic_statement

denotes

Due to the non-arbitrary strain selection no conclusion can be drawn considering the real prevalence of AIEC-like strains in the intestinal tract of animals, but their frequent detection provides support for a lack of host-specificity and a zoonotic risk.

T1454

822235-822550

Epistemic_statement

denotes

Further studies including well characterized diseased animals are needed in order to detect putative reservoirs of AIEC strains, even in the intestine of asymptomatic carriers, and to evaluate the dimension of the risk with respect to the implementation of prevention and control measures and thus to public health.

T1455

823492-823696

Epistemic_statement

denotes

These findings have implications in the pathogenesis of HUS, and suggest the existence of yet to be delineated Stx type-specific mechanisms of endothelial injury beyond inhibition of protein biosynthesis.

T1456

823697-823947

Epistemic_statement

denotes

Simultaneous detection of eight potential bioterrorism agents by real time PCR The Bacillus anthracis attacks in the United States in 2001 demonstrated the need of fast and reliable diagnostic methods for the detection of potential biological agents.

T1457

824428-824533

Epistemic_statement

denotes

However, an assay for the simultaneous detection of eight different agents has not been developed so far.

T1458

825389-825545

Epistemic_statement

denotes

In total we designed a real-time PCR TaqMan assay combination for the detection of eight different potential bioterrorism specimen in one real-time PCR run.

T1459

825546-825754

Epistemic_statement

denotes

This assay is easily to handle because of lyophilizied primers and probes and for the first time, it is possible to detect all these highly virulent pathogens at the same time with very good detection limits.

T1460

826317-826471

Epistemic_statement

denotes

The persister state is reversible and dormant cells might be expected to form stochastically during growth of a culture, prior to the antibiotic exposure.

T1461

827405-827513

Epistemic_statement

denotes

Challenging of HG001-003 with 10-fold tobramycin resulted in SCV-like cells upon cultivation on solid media.

T1462

827514-827664

Epistemic_statement

denotes

These results indicate that stationary-phase cells are more antibiotic tolerant than exponential-phase cells due to the elevated levels of persisters.

T1463

827665-827803

Epistemic_statement

denotes

Thus, growth phase as well as strain background and genotype appear to be important factors in the formation of S. aureus persister cells.

T1464

828215-828542

Epistemic_statement

denotes

of Immunology and Gnotobiology, Academy of Sciences of the Czech Republic, Novy Hradek, Czech Republic Background: The pattern recognition molecule NOD2 plays an important role in maintaining of intestinal homeostasis and mutation of the NOD2 gene has been associated in humans with increased susceptibility to Crohn's disease.

T1465

828694-829029

Epistemic_statement

denotes

However, several studies in mice have shown that NOD2 plays an important role in controlling the composition of the intestinal microbiota by regulating expression of antimicrobial peptides and in the host defense against several intestinal pathogens such as Yersinia pseudotuberculosis, Citrobacter rodentium or Helicobacter hepaticus.

T1466

830070-830249

Epistemic_statement

denotes

Conclusions: These results clearly demonstrate a link between E. faecalis stain specificity and the ability of this commensal to trigger disease in a genetically susceptible host.

CORD-19:4ca5d854d3f99440b507fd7dfae73c8ad6fc45d5 JSON TXT 9 Projects

Annnotations TAB TSV DIC JSON TextAE

CORD-19:4ca5d854d3f99440b507fd7dfae73c8ad6fc45d5 JSONTXT 9 Projects

Annnotations TAB TSV DIC JSON TextAE

CORD-19:4ca5d854d3f99440b507fd7dfae73c8ad6fc45d5 JSON TXT 9 Projects