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          Institute: MPI für Infektionsbiologie     Collection: Department of Molecular Biology     Display Documents



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ID: 529966.0, MPI für Infektionsbiologie / Department of Molecular Biology
A Global Overview of the Genetic and Functional Diversity in the Helicobacter pylori cag Pathogenicity Island
Authors:Olbermann, Patrick; Josenhans, Christine; Moodley, Yoshan; Uhr, Markus; Stamer, Christiana; Vauterin, Marc; Suerbaum, Sebastian; Achtman, Mark; Linz, Bodo
Language:English
Date of Publication (YYYY-MM-DD):2010-08
Title of Journal:PLoS Genetics
Journal Abbrev.:PLoS Genet.
Volume:6
Issue / Number:8
Sequence Number of Article:e1001069
Copyright:© 2010 Olbermann et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Review Status:Peer-review
Audience:Experts Only
Abstract / Description:The Helicobacter pylori cag pathogenicity island (cagPAI) encodes a type IV secretion system. Humans infected with cagPAI-carrying H. pylori are at increased risk for sequelae such as gastric cancer. Housekeeping genes in H. pylori show considerable genetic diversity; but the diversity of virulence factors such as the cagPAI, which transports the bacterial oncogene CagA into host cells, has not been systematically investigated. Here we compared the complete cagPAI sequences for 38 representative isolates from all known H. pylori biogeographic populations. Their gene content and gene order were highly conserved. The phylogeny of most cagPAI genes was similar to that of housekeeping genes, indicating that the cagPAI was probably acquired only once by H. pylori, and its genetic diversity reflects the isolation by distance that has shaped this bacterial species since modern humans migrated out of Africa. Most isolates induced IL-8 release in gastric epithelial cells, indicating that the function of the Cag secretion system has been conserved despite some genetic rearrangements. More than one third of cagPAI genes, in particular those encoding cell-surface exposed proteins, showed signatures of diversifying (Darwinian) selection at more than 5% of codons. Several unknown gene products predicted to be under Darwinian selection are also likely to be secreted proteins (e.g. HP0522, HP0535). One of these, HP0535, is predicted to code for either a new secreted candidate effector protein or a protein which interacts with CagA because it contains two genetic lineages, similar to cagA. Our study provides a resource that can guide future research on the biological roles and host interactions of cagPAI proteins, including several whose function is still unknown.
Comment of the Author/Creator:The work was financially supported by the German Federal Ministry for Education and Research (BMBF) in the framework of the competence center of the PathoGenoMik Network (Grant 03U213) and the ERAnet HELDIVnet program to MA, CJ, and SS; by the Sixth Research Framework Programme of the European Union, project INCA (LSHC-CT-2005-018704), to SS and CJ; and by Scientific Foundation of Ireland grant 05/FE1/B882 to MA.
External Publication Status:published
Document Type:Article
Communicated by:Hilmar Fünning
Affiliations:MPI für Infektionsbiologie/Department of Molecular Biology
External Affiliations:Hannover Med Sch, Inst Med Microbiol & Hosp Epidemiol, D-30623 Hannover, Germany.; Univ Coll Cork, Environm Res Inst, Cork, Ireland.; Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA 16802 USA.
Identifiers:ISI:000281383800024 [ID No:1]
ISSN:1553-7390 [ID No:2]
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