Phylogeographic origin of Helicobacter pylori is a determinant of gastric cancer risk

Sablet, Thibaut de; Piazuelo, M. Blanca; Shaffer, Carrie L.; Schneider, Barbara; Asim, Mohammad; Chaturvedi, Rupesh; Bravo, Luis Eduardo; Sicinschi, Liviu A.; Delgado, Alberto; Mera, Robertino; Israel, Dawn A.; Romero–Gallo, Judith; Peek, Richard M.; Cover, Timothy L.; Correa, Pelayo; Wilson, Keith T.

doi:10.1136/gut.2010.234468

Cited by 129 publications

(159 citation statements)

References 38 publications

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“…Among the strains included in this study, 35 had been previously analyzed by MLST, and whole-genome sequences were available from 8 other strains. MLST analysis was performed as previously described (19,37). In brief, partial nucleotide sequences of seven housekeeping genes (atpA, efp, mutY, ppa, trpC, ureI, and yphC) were compared to the corresponding sequences of 490 reference H. pylori strains that were previously classified into distinct groups (20,35,39).…”

Section: Methodsmentioning

confidence: 99%

J-Western Forms of Helicobacter pylori cagA Constitute a Distinct Phylogenetic Group with a Widespread Geographic Distribution

et al. 2012

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Chronic infection with Helicobacter pylori strains expressing the bacterial oncoprotein CagA confers an increased risk of gastric cancer. While much is known about the ancestry and molecular evolution of Western, East Asian, and Amerindian cagA sequences, relatively little is understood about a fourth group, known as "J-Western," which has been detected mainly in strains from Okinawa, Japan. We show here that J-Western cagA sequences have a more widespread global distribution than previously recognized, occur in strains with multiple different ancestral origins (based on multilocus sequence typing [MLST] analysis), and did not arise recently. As shown by comparisons of Western and J-Western forms of CagA, there are 45 fixed or nearly fixed amino acid differences, and J-Western forms contain a unique 4-amino-acid insertion. The mean nucleotide diversity of synonymous sites ( s ) is slightly lower in the J-Western group than in the Western and East Asian groups (0.066, 0.086, and 0.083, respectively), which suggests that the three groups have comparable, but not equivalent, effective population sizes. The reduced s of the J-Western group is attributable to ancestral recombination events within the 5= region of cagA. Population genetic analyses suggest that within the cagA region encoding EPIYA motifs, the East Asian group underwent a marked reduction in effective population size compared to the Western and J-Western groups, in association with positive selection. Finally, we show that J-Western cagA sequences are found mainly in strains producing m2 forms of the secreted VacA toxin and propose that these functionally interacting proteins coevolved to optimize the gastric colonization capacity of H. pylori.

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Section: Methodsmentioning

confidence: 99%

J-Western Forms of Helicobacter pylori cagA Constitute a Distinct Phylogenetic Group with a Widespread Geographic Distribution

et al. 2012

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“…Colombian populations in the high Andes have a higher incidence of gastric cancer associated with H. pylori, while coastal populations have a reduced incidence of gastric cancer (25). Multilocus sequence typing (MLST) analysis of Colombian H. pylori strains from these regions have revealed an association between strains from high-risk areas and ancestral European strains of H. pylori, while strains from low-risk regions are mostly associated phylogenetically with African strains (26). However, the mechanisms by which these genetic changes mediate greater virulence have not been characterized.…”

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confidence: 99%

Phylogeographic Origin of Helicobacter pylori Determines Host-Adaptive Responses upon Coculture with Gastric Epithelial Cells

et al. 2013

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g While Helicobacter pylori infects over 50% of the world's population, the mechanisms involved in the development of gastric disease are not fully understood. Bacterial, host, and environmental factors play a role in disease outcome. To investigate the role of bacterial factors in H. pylori pathogenesis, global gene expression of six H. pylori isolates was analyzed during coculture with gastric epithelial cells. Clustering analysis of six Colombian clinical isolates from a region with low gastric cancer risk and a region with high gastric cancer risk segregated strains based on their phylogeographic origin. One hundred forty-six genes had increased expression in European strains, while 350 genes had increased expression in African strains. Differential expression was observed in genes associated with motility, pathogenicity, and other adaptations to the host environment. European strains had greater expression of the virulence factors cagA, vacA, and babB and were associated with increased gastric histologic lesions in patients. In AGS cells, European strains promoted significantly higher interleukin-8 (IL-8) expression than did African strains. African strains significantly induced apoptosis, whereas only one European strain significantly induced apoptosis. Our data suggest that gene expression profiles of clinical isolates can discriminate strains by phylogeographic origin and that these profiles are associated with changes in expression of the proinflammatory and protumorigenic cytokine IL-8 and levels of apoptosis in host epithelial cells. These findings support the hypothesis that bacterial factors determined by the phylogeographic origin of H. pylori strains may promote increased gastric disease.

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“…25 In this study, we did not attempt to obtain such relations because of the low number of strains used for MLST analysis and the lack of clearly defined groups of low and high risk of gastric cancer. In Colombia the hpEurope strains induced more severe histologic alterations in the epithelium and greater DNA damage, independently of the subpopulation from which they were isolated, 25 and this phenomenon could also be partly responsible for the high cancer burden in Costa Rica, as hpEurope related strains are dominating.…”

Section: Discussionmentioning

confidence: 99%

The geographic origin ofHelicobacter pyloriisolated from Costa Rican patients

et al. 2014

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Phylogeographic origin of Helicobacter pylori is a determinant of gastric cancer risk

Cited by 129 publications

References 38 publications

J-Western Forms of Helicobacter pylori cagA Constitute a Distinct Phylogenetic Group with a Widespread Geographic Distribution

J-Western Forms of Helicobacter pylori cagA Constitute a Distinct Phylogenetic Group with a Widespread Geographic Distribution

Phylogeographic Origin of Helicobacter pylori Determines Host-Adaptive Responses upon Coculture with Gastric Epithelial Cells

The geographic origin ofHelicobacter pyloriisolated from Costa Rican patients

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