Journal
JOURNAL OF BACTERIOLOGY
Volume 192, Issue 23, Pages 6126-6135Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/JB.01081-10
Keywords
-
Categories
Funding
- National Institutes of Health [R01 AI39657, R01 AI068009, P01 CA116087, R01 GM085163]
- German Research Foundation [SFB 900/A1]
- Department of Veterans Affairs
- Burroughs Wellcome Fund
Ask authors/readers for more resources
Helicobacter pylori is a genetically diverse organism that is adapted for colonization of the human stomach. All strains contain a gene encoding a secreted, pore-forming toxin known as VacA. Genetic variation at this locus could be under strong selection as H. pylori adapts to the host immune response, colonizes new human hosts, or inhabits different host environments. Here, we analyze the molecular evolution of VacA. Phylogenetic reconstructions indicate the subdivision of VacA sequences into three main groups with distinct geographic distributions. Divergence of the three groups is principally due to positively selected sequence changes in the p55 domain, a central region required for binding of the toxin to host cells. Divergent amino acids map to surface-exposed sites in the p55 crystal structure. Comparative phylogenetic analyses of vacA sequences and housekeeping gene sequences indicate that vacA does not share the same evolutionary history as the core genome. Further, rooting the VacA tree with outgroup sequences from the close relative Helicobacter acinonychis reveals that the ancestry of VacA is different from the African origin that typifies the core genome. Finally, sequence analyses of the virulence determinant CagA reveal three main groups strikingly similar to the three groups of VacA sequences. Taken together, these results indicate that positive selection has shaped the phylogenetic structure of VacA and CagA, and each of these virulence determinants has evolved separately from the core genome.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available