Epistemic_Statements  

CORD-19:e6e0128e5f23630f1be605cb1a7fb4cc8261f323 JSONTXT 8 Projects

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Id Subject Object Predicate Lexical cue
T1 0-119 Epistemic_statement denotes Under the microscope: From pathogens to probiotics and back Under the microscope: From pathogens to probiotics and back
T2 130-413 Epistemic_statement denotes The review centers on the human gastrointestinal tract; focusing first on the bacterial stress responses needed to overcome the physiochemical defenses of the host, specifically how these stress survival strategies can be used as targets for alternative infection control strategies.
T3 1202-1438 Epistemic_statement denotes My research career began with a focus on bacterial stress responses; determining how bacteria overcome the various stresses encountered in food production/storage and subsequently, following ingestion, within the gastrointestinal tract.
T4 2272-2401 Epistemic_statement denotes Barotolerance -the ability to overcome pressures in excess of 300 MPa, associated with high pressure processing of certain foods.
T5 2402-2527 Epistemic_statement denotes The first significant challenge encountered by gastrointestinal pathogens, following ingestion, is the low pH of the stomach.
T6 2730-2837 Epistemic_statement denotes 1 Mutation analysis revealed a role for htrA in acid tolerance and virulence potential in L. monocytogenes.
T7 3009-3156 Epistemic_statement denotes 2 Originally identified as an acid tolerance locus and listerial virulence factor, LisRK is also linked to b-lactam resistance in L. monocytogenes.
T8 3231-3427 Epistemic_statement denotes 2 Indeed, mutational analysis revealed that in addition to regulating HtrA, LisRK likely controls the transcription of one or more additional systems necessary for optimal listerial osmotolerance.
T9 3428-3627 Epistemic_statement denotes Furthermore, it appears that LisRK may act at the initial stages of the listerial osmotic stress-response, with LisK possibly functioning as the primary sensor and LisR (and its genetic targets, e.g.
T10 3687-3894 Epistemic_statement denotes LisRK may thus represent a new dimension in the osmosensing and osmoregulatory capabilities of L. monocytogenes, functioning independently of, but in tandem with, osmolyte uptake synthesis (described below).
T11 3927-4057 Epistemic_statement denotes In the late 1990s, knowledge of the listerial osmotolerance response was limited; confined mainly to physiological investigations.
T12 4390-4664 Epistemic_statement denotes Representing the first genetic analysis of osmotolerance in Listeria, this study also identified a putative s B -dependent promoter binding site upstream of betL, suggesting that betaine uptake in Listeria might be regulated, at least in part, at the level of transcription.
T13 4665-4803 Epistemic_statement denotes Indeed, we later proved the hypothesis, recording a 1.6-fold increase in betL transcript levels following exposure to elevated osmolarity.
T14 5130-5311 Epistemic_statement denotes Rapid activation of pre-existing BetL, in response to relatively low NaCl concentrations, suggested that the protein is one of the primary respondents to rapid fluxes in osmolarity.
T15 5312-5521 Epistemic_statement denotes 6 Furthermore, in addition to transcriptional and post-translational control, in silico analysis strongly suggests a role for translational control, not only of betL but of listerial osmoregulation in general.
T16 5522-5737 Epistemic_statement denotes 7 However, despite its obvious role in listerial osmotolerance, deleting betL did not significantly impair growth of the pathogen at elevated osmolarity; suggesting the existence of multiple osmolyte uptake systems.
T17 5738-5939 Epistemic_statement denotes In support of this, we described the identification and characterization of OpuC, a carnitine uptake system which contributes to osmotolerance, chill stress and virulence potential of L. monocytogenes.
T18 5940-6211 Epistemic_statement denotes 8, 9 Indeed, Sleator et al., 8 provided the first direct link between osmotolerance and virulence in Listeria, a link which we ascribed to the accumulation of carnitine, a protective compound similar to betaine but present at much higher concentrations in animal tissues.
T19 6868-7016 Epistemic_statement denotes Interestingly, while betaine appeared to confer most protection in food, the hierarchy of transporter importance differs depending on the food type.
T20 7017-7156 Epistemic_statement denotes While in the animal model, OpuC appears to play the dominant role, with the remaining systems contributing little to the infection process.
T21 8138-8290 Epistemic_statement denotes 15 However, as observed for proline auxotrophy, proline hyperproduction has no apparent impact on listerial osmotolerance or indeed virulence potential.
T22 8595-8752 Epistemic_statement denotes 16 Furthermore, the mutation appears to counter a previously unreported "twisted" cell morphology observed for L. monocytogenes grown at elevated osmolarity.
T23 9163-9262 Epistemic_statement denotes My interest in osmotolerance did not end however with the conclusion of the Listeria story in 2001.
T24 9665-9771 Epistemic_statement denotes Unravelling C. sakazakii' s osmotolerance mechanisms is thus a key first step in controlling the pathogen.
T25 10055-10387 Epistemic_statement denotes 20 Interestingly, while C. sakazakii contains homologs of all the principal E. coli osmotolerance loci; a key distinguishing feature is that C. sakazakii possesses multiple copies of certain osmotolerance genes; including seven copies of the E. coli proP homolog, each of which potentially encodes a separate osmolyte uptake system.
T26 10860-11093 Epistemic_statement denotes Further structural analysis of the C. sakazakii ProP homologs revealed that all but one (ProP1, which offers the greatest osmoprotective effect) are 60-70 amino acids shorter than the E. coli ProP; lacking the extended carboxyl tail.
T27 11094-11206 Epistemic_statement denotes This immediately suggested a role for the C-terminal domain in modulating the protein's osmoprotective function.
T28 11207-11476 Epistemic_statement denotes This hypothesis was proved by spicing the extended C-terminal domain of ProP1 (encoded by ESA_02131) onto the truncated C-terminal end of ProP2 (encoded by ESA_01706); creating a chimeric protein (ProPc) which exhibits increased osmotolerance relative to the wild type.
T29 12605-12745 Epistemic_statement denotes This represents a viable alternative to antibiotic therapy and may lead to effective control of the pathogen in high risk foods such as PIF.
T30 13647-13858 Epistemic_statement denotes Each of the three genes identified was found to be over-represented in the human gut metagenome and abundant among healthy subjects from the MetaHit data set, 24 suggesting an important role in gut colonisation.
T31 14733-14914 Epistemic_statement denotes In support of this, we describe the identification and subsequent analysis of an unknown gene (stlA, for "salt tolerance locus A") with no currently known homologs in the databases.
T32 14915-15155 Epistemic_statement denotes 32 The stlA gene is rare when searched against the human metagenome datasets, MetaHit and the Human Microbiome Project, and represents a novel and unique salt tolerance determinant which is apparently exclusive to the human gut environment.
T33 15363-15681 Epistemic_statement denotes 18 Despite exhibiting significant sequence similarity to the betaine carnitine choline transporter (BCCT) family, further analysis suggested that the protein most likely functions as a bile efflux pump (actively extruding toxic bile out of the cell), a conclusion substantiated by radiolabelled bile exclusion studies.
T34 15682-15918 Epistemic_statement denotes In addition, functionally inactivating BilE resulted in a significantly increased sensitivity to physiological concentrations of human bile, and a reduction in virulence potential when administered orally to a murine model of infection.
T35 16321-16559 Epistemic_statement denotes 34 While deletion mutants revealed a role for all three genes in resisting the acute toxicity of bile, hydrolysis assays indicated that BSH is likely the only listerial bile salt hydrolase (leading to bile detoxification inside the cell).
T36 16682-16847 Epistemic_statement denotes The fact that both bilE and bsh are controlled by s B , along with betL, gbu and opuC (which also boasts a PrfA box), suggested a common function for all 4 proteins.
T37 16848-17046 Epistemic_statement denotes 35 In support of this hypothesis, a systematic analysis of strains with mutations in BetL, OpuC and Gbu revealed roles for OpuC, and to a lesser extent BetL, in resisting the acute toxicity of bile.
T38 17711-17848 Epistemic_statement denotes However, a low-pH challenge (as experienced during gastric transit) fails to similarly protect against subsequent osmotic or bile stress.
T39 17917-18032 Epistemic_statement denotes Thus, osmotic stress appears to be at the top of the hierarchy of stress responses during gastrointestinal transit.
T40 18033-18302 Epistemic_statement denotes 38, 39 Given that sigB is transcriptionally upregulated at elevated osmolarity, it is likely that the increased osmolarity of the gastrointestinal lumen may be interpreted by L. monocytogenes as an environmental cue, signaling gut entry (as is the case for Salmonella).
T41 18303-18801 Epistemic_statement denotes 40 Furthermore, given that s B is known to modulate expression of prfA (the master regulator of the virulence gene cluster which coordinates the intracellular phase of L. monocytogenes infection) it is possible that osmotically induced stimulation of the s B regulon in the upper small intestine may not only facilitate successful gastrointestinal transit, but also prime the pathogen for the next phase of infection, which, in susceptible individuals, is the systemic invasive disease listeriosis.
T42 18802-18974 Epistemic_statement denotes 41 Barotolerance Prior to ingestion, gastrointestinal pathogens are often subject to a variety of hostile conditions; particularly stresses associated with food processing.
T43 19140-19344 Epistemic_statement denotes Indeed, in Considine et al., 42 we outline how HPP can inactivate microorganisms and enzymes and modify macromolecular structures, with little or no impact on the nutritional and sensory quality of foods.
T44 20353-20574 Epistemic_statement denotes In an interesting link with previous sections, and substantiating a role for osmolytes as a listerial passe-partout, 45 both osmolyte uptake and synthesis systems have been shown to play a role in listerial barotolerance.
T45 20954-21190 Epistemic_statement denotes With a mission statement "linking Irish science with industry and society through excellence in research, education and outreach in gastrointestinal health," the APC is arguably one of the world's leading centers of gut health research.
T46 22009-22256 Epistemic_statement denotes [56] [57] [58] [59] [60] This approach showed promise not only for the design of more technologically robust probiotic cultures, with improved biotechnological applications, but also in the development of novel vaccine and drug delivery platforms.
T47 22257-22650 Epistemic_statement denotes In support of this, Sheehan et al., 61 describes how heterologous expression of the listerial betL gene in Lactobacillus salivarius significantly increased resistance of the probiotic to several ex vivo stresses, including elevated osmo-, cryo-, baro-, and chill tolerance, as well as increased resistance to spray-and freeze-drying (stresses associated with food processing and preservation).
T48 23275-23495 Epistemic_statement denotes 62 These physiologically enhanced probiotics function as ideal drug and vaccine delivery platforms; 63 targeting difficult to treat pathogens such as Clostridium difficile, 64 Acinetobacter baumannii 65 and Mycobacteria.
T49 23876-24027 Epistemic_statement denotes This construct allowed us, for the first time, to track the colonisation potential and persistence of the probiotic in real time in live animal models.
T50 24028-24262 Epistemic_statement denotes Indeed, a significant outcome of the study was the identification of the cecum as a niche environment for B. breve; a finding which may explain why appendectomies may lead to an increased risk of functional gastrointestinal disorders.
T51 24263-24266 Epistemic_statement denotes 70
T52 24267-24363 Epistemic_statement denotes Molecular diagnostics is arguably one of the fastest growing areas in gastrointestinal research.
T53 25387-25578 Epistemic_statement denotes This represents the first report of C. ureolyticus in the faeces of patients presenting with gastroenteritis, suggesting a heretofore unreported role for this organism as an enteric pathogen.
T54 26019-26319 Epistemic_statement denotes Given that cultural isolation of C. ureolyticus was not possible using the established selective methods for the isolation of Campylobacter spp., we were forced to develop a new selective medium, nalidixic acid amphotericin B vancomycin (NAV), capable of isolating C. ureolyticus from faecal samples.
T55 26320-26478 Epistemic_statement denotes 76 This medium made it possible, for the first time, to isolate pure cultures of C. ureolyticus and to determine the potential source of infections in humans.
T56 26866-27053 Epistemic_statement denotes Together with the findings of Koziel et al.,, 75 which reported the detection of C. ureolyticus in bovine samples, it appeared likely that this emerging pathogen has a zoonotic potential.
T57 27054-27226 Epistemic_statement denotes Whole genome sequence analysis of CIT 007 appeared to confirm this hypothesis; identifying a number of genetic loci necessary to cause gastrointestinal infection in humans.
T58 27422-27641 Epistemic_statement denotes Furthermore, this analysis also suggested that C. ureolyticus is likely to exist as a taxonomic continuum comprised of several species (genomospecies) that are likely to have varying impacts on human health and disease.
T59 27813-28118 Epistemic_statement denotes Originally believed to be C. ureolyticus on the basis of colony morphology; 16S rRNA analysis showed it to be a completely new Campylobacter species; 80 a finding which we confirmed using matrix-assisted laser desorption/ionization time of flight (MALDI-TOF), together with whole genome sequence analysis.
T60 29732-29932 Epistemic_statement denotes This is particularly relevant given that shifting genotype prevalence, the emergence of novel combinations and mixed infections, are all likely to impact negatively on existing vaccination programmes.
T61 29933-29991 Epistemic_statement denotes In extreme cases this can lead to breakthrough infections.
T62 30391-30679 Epistemic_statement denotes Recognizing the potential of biology's big data sets in developing improved diagnostic techniques, our lab began to focus on phylogenetics, 87,88 genomics, [89] [90] [91] [92] protein structure/function prediction [93] [94] [95] [96] [97] [98] and the emerging field of synthetic biology.