PMC:3091627 / 2005-6368 JSONTXT

{"project":"2_test","denotations":[{"id":"20537153-14755326-10781708","span":{"begin":163,"end":164},"obj":"14755326"},{"id":"20537153-2059685-10781709","span":{"begin":231,"end":232},"obj":"2059685"},{"id":"20537153-6336974-10781710","span":{"begin":366,"end":367},"obj":"6336974"},{"id":"20537153-11556297-10781711","span":{"begin":560,"end":561},"obj":"11556297"},{"id":"20537153-12197905-10781712","span":{"begin":739,"end":740},"obj":"12197905"},{"id":"20537153-9135515-10781713","span":{"begin":912,"end":913},"obj":"9135515"},{"id":"20537153-3385767-10781714","span":{"begin":1095,"end":1096},"obj":"3385767"},{"id":"20537153-15759043-10781715","span":{"begin":1246,"end":1247},"obj":"15759043"},{"id":"20537153-9430586-10781716","span":{"begin":1381,"end":1382},"obj":"9430586"},{"id":"20537153-12142529-10781717","span":{"begin":1391,"end":1393},"obj":"12142529"},{"id":"20537153-12377603-10781718","span":{"begin":1402,"end":1404},"obj":"12377603"},{"id":"20537153-19545429-10781719","span":{"begin":1413,"end":1415},"obj":"19545429"},{"id":"20537153-15716466-10781720","span":{"begin":1535,"end":1537},"obj":"15716466"},{"id":"20537153-15557006-10781721","span":{"begin":1634,"end":1636},"obj":"15557006"},{"id":"20537153-16027366-10781722","span":{"begin":1637,"end":1639},"obj":"16027366"},{"id":"20537153-11865403-10781723","span":{"begin":1864,"end":1866},"obj":"11865403"},{"id":"20537153-12560462-10781724","span":{"begin":2056,"end":2058},"obj":"12560462"},{"id":"20537153-14742532-10781725","span":{"begin":2082,"end":2084},"obj":"14742532"},{"id":"20537153-19806222-10781726","span":{"begin":2085,"end":2087},"obj":"19806222"},{"id":"20537153-9252185-10781727","span":{"begin":2650,"end":2652},"obj":"9252185"},{"id":"20537153-16788065-10781728","span":{"begin":2768,"end":2770},"obj":"16788065"},{"id":"20537153-18952803-10781729","span":{"begin":2808,"end":2810},"obj":"18952803"},{"id":"20537153-11121067-10781730","span":{"begin":3054,"end":3056},"obj":"11121067"},{"id":"20537153-16217547-10781731","span":{"begin":3400,"end":3402},"obj":"16217547"},{"id":"20537153-18493595-10781732","span":{"begin":3640,"end":3642},"obj":"18493595"}],"text":"Background\nHelicobacter pylori infections occur in approximately 50% of the human population and are associated with several inflammatory gastroduodenal diseases [1], including two types of gastric cancers: gastric adenocarcinoma [2] and gastric extra-nodal marginal zone B-cell MALT (mucosa-associated lymphoid tissue) lymphoma, first described by Isaacson et al. [3]. Evolution of this bacterial infection towards malignancy only occurs in approximately 1% of infected individuals, suggesting that both bacterial and host susceptibility factors are involved[4].\nSince the discovery of H. pylori, several studies have focused on elucidating H. pylori pathogenicity mechanisms (microbial factors) that are associated with disease outcomes[5]. The cag-pathogenicity island (cagPAI) has been recognized as a major pro-inflammatory actor, but its association with MALT lymphoma strains has yet to be clearly shown [6]. The VacA vacuolating cytotoxin, thought to cause detectable alterations in gastric epithelial cells and immune cells, is also one of the most studied H. pylori virulence factors [7]. VacA has also been suggested to play a role in H. pylori persistence, demonstrated by in vitro studies, based on its immunosuppressive properties [8]. Adhesion of H. pylori to gastric epithelial cells is another bacterial trait contributing to chronic state of the infection. BabA [9], SabA [10], HopZ [11], HomB [12] and 30 outer-membrane-like paralogs recognized as adhesins or potential adhesins are encoded by the H. pylori genome [13]. Several studies have highlighted their contribution to pathogen fitness in human populations [14,15]. Over the last twenty years, genes encoding these virulence factors have served as genotyping markers to establish correlations between these markers, alone or in combination, and clinical outcomes of H. pylori infections [16].\nFew studies have been conducted in relation to gastric MALT lymphoma-associated strains. Koehler et al. reported that the vacAm2 allele predominated in MALT lymphoma-associated isolates [17]. In previous studies [18,19] including an identical collection of H. pylori gastric MALT lymphoma strains to that used here, the authors confirmed this finding and suggested that certain combinations of genomic markers may have a predictive value for determining whether gastric MALT lymphoma develops. All these data suggest the potential role for bacterial determinism in the clinical outcome of MALT lymphoma.\nSo far, comparative genomics involving sequenced H. pylori genomes have been limited to five clinical isolates isolated in the West and associated with gastritis [strain 26695 [20], peptic ulcers (strains J99 [GenBank:AE001439.1], P12 [EMBL:CP001217, EMBL:CP001218]), atrophic gastritis (HPAG1 [21]), or no known disease (strains G27 [22] and Shi470 [RefSeq:NC_010698]. However, no genome sequence of a H. pylori strain isolated from MALT lymphoma is currently available. Comparative genomics based on DNA-array analyses, first conducted by Salama et al. on 15 Caucasian isolates [23], led to the elucidation of the H. pylori core genome comprising the pool of ubiquitous H. pylori genes and strain-specific genes (non-ubiquitous). Gressmann et al. studied gene gain and loss during evolution, by comparing the genome of 56 globally representative strains of H. pylori; they reported that 25% of the genes were non-ubiquitous [24]. Through comparative genomics based on the analysis of 24 clinical isolates from various geographical origins (Western, Asian, African countries) using whole genome DNA arrays, we identified 213 non-ubiquitous or strain-specific genes [25]. In this study, we describe the gene distribution of these 213 non-ubiquitous genes (Additional file 1) within genomes from a large geographically homogeneous French collection of 120 well-characterized H. pylori strains associated with chronic gastritis, duodenal ulcer, intestinal metaplasia or gastric MALT lymphoma. A hierarchical clustering analysis of the DNA hybridization values identified a homogeneous phylogenic subpopulation of strains containing all of the cagPAI minus MALT lymphoma isolates. The B38 isolate was selected as a representative of this MALT lymphoma-specific cluster. Its genome sequence was completed, fully annotated, and compared with previously sequenced and published H. pylori genomes."}