Helicobacter pylori strain-specific differences in genetic content, identified by microarray, influence host inflammatory responses
Dawn A. Israel, Nina Salama, Carrie N. Arnold, Steven F. Moss, Takafumi Ando, Hans-Peter Wirth, Kyi T. Tham, Margorita Camorlinga, Martin J. Blaser, Stanley Falkow, Richard M. Peek Jr.
Dawn A. Israel, Nina Salama, Carrie N. Arnold, Steven F. Moss, Takafumi Ando, Hans-Peter Wirth, Kyi T. Tham, Margorita Camorlinga, Martin J. Blaser, Stanley Falkow, Richard M. Peek Jr.
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Helicobacter pylori strain-specific differences in genetic content, identified by microarray, influence host inflammatory responses

Abstract

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.

Authors

Dawn A. Israel, Nina Salama, Carrie N. Arnold, Steven F. Moss, Takafumi Ando, Hans-Peter Wirth, Kyi T. Tham, Margorita Camorlinga, Martin J. Blaser, Stanley Falkow, Richard M. Peek Jr.

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Quantitation of IL-8 and analysis of apoptosis among preinoculation (par...
Quantitation of IL-8 and analysis of apoptosis among preinoculation (parental) strains B128 and G1.1 (a) and their derivative progeny after gerbil passage (b). (a) AGS cells were grown alone or in the presence of H. pylori GU strain B128 (filled columns) or DU strain G1.1 (open columns). IL-8 concentrations were determined 24 hours after inoculation by ELISA. No 48-hour samples were analyzed due to the significant loss of AGS cell viability that had occurred by this time point. Cell viability and apoptosis were assessed by trypan blue exclusion and DNA fragmentation ELISA, respectively, 24 and 48 hours following inoculation. Results are expressed as the percent change in IL-8, viability, or apoptosis relative to controls. Data represent mean ± SD of three independent experiments. AP ≤ 0.05 compared with AGS cells alone. BP ≤ 0.05 compared with controls or with DU strain G1.1. (b) Six gerbil-passaged B128 and G1.1 isolates were selected (B128-A and G1.1-A, 2 weeks; B128-B and G1.1-B, 6–12 weeks; B128-C and G1.1-C, 16–20 weeks after challenge, respectively). Apoptosis results are expressed as levels of nucleosomal release relative to controls. IL-8 concentrations are expressed as pg/ml. Bars, SD.