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A global overview of the genetic and functional diversity in the helicobacter pylori cag pathogenicity island
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Malik, Harmit S., Olbermann, Patrick, Josenhans, Christine, Moodley, Yoshan, Uhr, Markus, Stamer, Christiana, Vauterin, Marc, Suerbaum, Sebastian, Achtman, Mark and Linz, Bodo (2010) A global overview of the genetic and functional diversity in the helicobacter pylori cag pathogenicity island. PLoS Genetics, Volume 6 (Number 8). Article Number e1001069. doi:10.1371/journal.pgen.1001069
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Official URL: http://dx.doi.org/10.1371/journal.pgen.1001069
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.
| Item Type: | Journal Article | ||||
|---|---|---|---|---|---|
| Divisions: | Faculty of Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Metabolic and Vascular Health (- until July 2016) Faculty of Medicine > Warwick Medical School Faculty of Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine Faculty of Medicine > Warwick Medical School > Biomedical Sciences > Microbiology & Infection |
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| Journal or Publication Title: | PLoS Genetics | ||||
| Publisher: | Public Library of Science | ||||
| ISSN: | 1553-7390 | ||||
| Official Date: | 2010 | ||||
| Dates: |
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| Volume: | Volume 6 | ||||
| Number: | Number 8 | ||||
| Article Number: | Article Number e1001069 | ||||
| DOI: | 10.1371/journal.pgen.1001069 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Restricted or Subscription Access | ||||
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