Helicobacter pylori produces acute superficial
gastritis in nearly all of its human hosts. However, a subset of individuals develops chronic
atrophic gastritis (
ChAG), a condition characterized in part by diminished numbers of
acid-producing parietal cells and increased risk for development of gastric
adenocarcinoma. Previously, we used a gnotobiotic transgenic mouse model with an engineered ablation of parietal cells to show that loss of parietal cells provides an opportunity for a H. pylori isolate from a patient with
ChAG (HPAG1) to bind to, enter, and persist within gastric stem cells. This finding raises the question of how
ChAG influences H. pylori genome evolution, physiology, and
tumorigenesis. Here we describe the 1,596,366-bp HPAG1 genome. Custom HPAG1 Affymetrix GeneChips, representing 99.6% of its predicted ORFs, were used for whole-genome genotyping of additional H. pylori
ChAG isolates obtained from Swedish patients enrolled in a case-control study of
gastric cancer, as well as
ChAG- and
cancer-associated isolates from an individual who progressed from
ChAG to gastric
adenocarcinoma. The results reveal a shared gene signature among
ChAG strains, as well as genes that may have been lost or gained during progression to
adenocarcinoma. Whole-genome transcriptional profiling of HPAG1's response to
acid during in vitro growth indicates that genes encoding components of
metal uptake and utilization pathways, outer
membrane proteins, and
virulence factors are among those associated with H. pylori's adaptation to
ChAG.