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

Israel DA, Salama N, Arnold CN, Moss SF, Ando T, Wirth HP, Tham KT, Camorlinga M, Blaser MJ, Falkow S, Peek RM
J Clin Invest. 2001 107 (5): 611-20

PMID: 11238562 · PMCID: PMC199426 · DOI:10.1172/JCI11450

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 microarray to identify bacterial determinants related to pathogenesis. Gastric ulcer strain B128 induced more severe gastritis, proliferation, and apoptosis in gerbil mucosa than did duodenal ulcer strain G1.1, and gastric ulceration and atrophy occurred only in B128+ gerbils. In vitro, gerbil-passaged B128 derivatives significantly increased IL-8 secretion and apoptosis compared with G1.1 strains. DNA hybridization to the microarray identified several strain-specific differences in gene composition including a large deletion 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 in vitro and significantly decreased gastric inflammation in vivo. These results indicate that the ability of H. pylori to regulate epithelial cell responses related to inflammation depends on the presence of an intact cag pathogenicity island. Use of an H pylori whole genome microarray is an effective method to identify differences in gene content between H. pylori strains that induce distinct pathological outcomes in a rodent model of H. pylori infection.

MeSH Terms (19)

Animals Antigens, Bacterial Apoptosis Bacterial Proteins Cell Division Cell Line Duodenal Ulcer Gastric Mucosa Gastritis Genome, Bacterial Gerbillinae Helicobacter Infections Helicobacter pylori Humans Inflammation Interleukin-8 Oligonucleotide Array Sequence Analysis Sequence Deletion Stomach Ulcer

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