The complete genome sequence of a chronic atrophic gastritis Helicobacter pylori strain: evolution during disease progression.

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.

Interactions between gastric epithelial stem cells and Helicobacter pylori in the setting of chronic atrophic gastritis.

Chronic atrophic gastritis (ChAG), a Helicobacter pylori-associated risk factor for the development of gastric cancer, involves loss of acid-producing parietal cells. Recent studies in gnotobiotic mouse models of ChAG have shown that parietal cell loss results in amplification of multi- and oligo-potential gastric stem cells that express sialylated glycan receptors recognized by H. pylori adhesins. Moreover, H. pylori resides within a subset of these stem cells. Studies of the transcriptomes of gastric stem cells, harvested directly from the stomachs of uninfected mice, using laser capture microdissection, suggest that they have the ability to complement some of the metabolic needs of H. pylori. These findings indicate that proliferating and non-proliferating gastric stem cells provide a habitat that could support H. pylori persistence in a gastric ecosystem that has lost its acid barrier to colonization by environmental, oral and intestinal microbes. One consequence to the host might be an increased risk of tumorigenesis.