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  A Global Overview of the Genetic and Functional Diversity in the Helicobacter pylori cag Pathogenicity Island

Olbermann, P., Josenhans, C., Moodley, Y., Uhr, M., Stamer, C., Vauterin, M., et al. (2010). A Global Overview of the Genetic and Functional Diversity in the Helicobacter pylori cag Pathogenicity Island. PLoS Genetics, 6(8): e1001069.

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Genre: Journal Article
Alternative Title : PLoS Genet.

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PLoS_Genet_2010_6_e1001069.pdf (Publisher version), 3MB
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© 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.
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 Creators:
Olbermann, Patrick, Author
Josenhans, Christine, Author
Moodley, Yoshan1, Author              
Uhr, Markus, Author
Stamer, Christiana1, Author              
Vauterin, Marc, Author
Suerbaum, Sebastian, Author
Achtman, Mark1, Author              
Linz, Bodo1, Author              
Affiliations:
1Department of Molecular Biology, Max Planck Institute for Infection Biology, Max Planck Society, ou_1664147              

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 Abstract: 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.

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Language(s): eng - English
 Dates: 2010-08
 Publication Status: Published in print
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 Rev. Type: Peer
 Identifiers: eDoc: 529966
ISI: 000281383800024
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Title: PLoS Genetics
  Alternative Title : PLoS Genet.
Source Genre: Journal
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Pages: - Volume / Issue: 6 (8) Sequence Number: e1001069 Start / End Page: - Identifier: ISSN: 1553-7390