Sequencing, annotation, and comparative genome analysis of the gerbil-adapted Helicobacter pylori strain B8

The Mongolian gerbils are a good model to mimic the Helicobacter pylori-associated pathogenesis of the human stomach. In the current study the gerbil-adapted strain B8 was completely sequenced, annotated and compared to previous genomes, including the 73 supercontigs of the parental strain B128.

The complete genome of H. pylori B8 was manually curated gene by gene, to assign as much function as possible. It consists of a circular chromosome of 1,673,997 bp and of a small plasmid of 6,032 bp carrying nine putative genes. The chromosome contains 1,711 coding sequences, 293 of which are strain-specific, coding mainly for hypothetical proteins, and a large plasticity zone containing a putative type-IV-secretion system and coding sequences with unknown function. The cag-pathogenicity island is rearranged such that the cagA-gene is located 13,730 bp downstream of the inverted gene cluster cagB-cag1. Directly adjacent to the cagA-gene, there are four hypothetical genes and one variable gene with a different codon usage compared to the rest of the H. pylori B8-genome. This indicates that these coding sequences might be acquired via horizontal gene transfer.The genome comparison of strain B8 to its parental strain B128 delivers 425 unique B8-proteins. Due to the fact that strain B128 was not fully sequenced and only automatically annotated, only 12 of these proteins are definitive singletons that might have been acquired during the gerbil-adaptation process of strain B128.

Our sequence data and its analysis provide new insight into the high genetic diversity of H. pylori-strains. We have shown that the gerbil-adapted strain B8 has the potential to build, possibly by a high rate of mutation and recombination, a dynamic pool of genetic variants (e.g. fragmented genes and repetitive regions) required for the adaptation-processes. We hypothesize that these variants are essential for the colonization and persistence of strain B8 in the gerbil stomach during in ammation.