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Title: Repeat-associated plasticity in the Helicobacter pylori RD Gene Family

Author
item SHAK, JOSHUA - Emory University
item DICK, JONATHAN - New York University School Of Medicine
item Meinersmann, Richard - Rick
item PEREZ-PEREZ, GUILLERMO - New York University School Of Medicine
item BLASER, MARTIN - New York University School Of Medicine

Submitted to: Journal of Bacteriology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/3/2009
Publication Date: 11/28/2009
Citation: Shak, J.R., Dick, J.J., Meinersmann, R.J., Perez-Perez, G.I., Blaser, M.J. 2009. Repeat-associated plasticity in the Helicobacter pylori RD Gene Family. Journal of Bacteriology. 191(22):6900-6910.

Interpretive Summary: Helicobacter pylori is one of the few bacteria able to survive in the acidic environment of the stomach, and previous studies have revealed a remarkable amount of genetic diversity between isolates. H. pylori serves as a model for studying diversification mechanisms in bacteria. Since DNA which repeats itself (repetitive DNA) is a condition that promotes genetic diversity, we hypothesized that the identification of regions of the genome with increased frequency of repetitive DNA would reveal genes that contribute to H. pylori survival. We discovered that numerous H. pylori DNA repeats are concentrated in a family of genes that are expressed at the bacterial cell surface. Although the location of these proteins exposes them to the immune system, we found no consistent recognition of this protein by serum from colonized hosts. These results indicate that this gene family, rich in repetitive DNA, may be involved in a mechanism that allows H. pylori to inhabit the human stomach for decades without provoking a sterilizing immune response.

Technical Abstract: epetitive DNA facilitates genomic flexibility via increased recombination, deletion, and insertion. The bacterium Helicobacter pylori is remarkable for its ability to persist in the human stomach for decades without provoking sterilizing immunity. Examining the genomes of two H. pylori strains, we discovered a family of genes with extensive repetitive DNA that we have termed the H. pylori RD gene family. Each gene of this family is composed of a 3' conserved region, a middle variable region composed of 7 and 11 amino acid repeats, and a 5' region containing one of two possible alleles. Analysis of five complete genome sequences and PCR genotyping of 42 H. pylori strains revealed extensive variation between strains in the number, location, and arrangement of RD genes. Furthermore, examination of multiple strains isolated from a single subject's stomach revealed intra-host variation in repeat number and composition. Despite prior evidence that the protein products of this gene family are expressed at the bacterial cell surface, ELISA and immunoblot studies revealed no consistent immunoreactivity to recombinant RD protein by H. pylori-positive hosts. The pattern of repeats uncovered in the RD gene family appears to reflect domain duplication, allowing for redundancy and subsequent diversity in genotype and phenotype. This novel family of hypervariable genes with both conserved and variable domains represents important candidates for understanding H. pylori persistence in its natural host.