Helicobacter pylori strain-specific differences in genetic content, identified by microarray, influence host inflammatory responses

Helicobacter pylori enhances the risk for ulcer disease and gastric cancer, yet only a minority of H. pylori-colonized individuals develop disease. We examined the ability of two H. pylori isolates to induce differential host responses in vivo or in vitro, and then used an H, pylori whole genome mic roarray to identify bacterial determinants related to pathogenesis. Gastric ulcer strain B128 induced more severe gastritis, proliferation, and apopto sis in gerbil mucosa than did duodenal ulcer strain G1.1, and gastric ulcer ation and atrophy occurred only in B128(+) gerbils. In vitro, gerbil-passag ed B128 derivatives significantly increased IL-8 secretion and apoptosis co mpared with G1.1 strains. DNA hybridization to the microarray identified se veral st-rain-specific differences in gene composition including a large de letion of the cag pathogenicity island in strain G1.1. Partial and complete disruption of the cag island in strain B128 attenuated induction of IL-8 i n vitro and significantly decreased gastric inflammation in vivo. These res ults indicate that the ability of H. pylori to regulate epithelial cell res ponses related to inflammation depends on the presence of an intact cag pat hogenicity island. Use of an H. pylori whole genome microarray is an effect ive method to identify differences in gene content between H. pylori strain s that induce distinct pathological outcomes in a rodent model of H. pylori infection.