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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H. pylori strains differentially alter gastric epithelial cell apoptosis...
H. pylori strains differentially alter gastric epithelial cell apoptosis (a) and proliferation (b) in Mongolian gerbil gastric mucosa. Apoptosis and proliferation scores at each time point are expressed as mean number of positive cells per gland in infected gerbils divided by mean scores in uninfected gerbils. Therefore, a value of 1 represents baseline. (a) Apoptosis scores were significantly higher in animals infected with GU strain B128 in the antrum (B128A; filled circles) and corpus (B128C; filled squares) 1–24 weeks after challenge compared with DU strain G1.1 (open symbols) or controls (P = 0.01 and 0.009, respectively); scores subsequently decreased, and by 26–52 weeks, they were not different from controls. Compared with uninfected animals, apoptosis was also significantly increased in gerbils infected with DU strain G1.1 but only in the antrum (G1.1A, open circles) and only at 2–4 weeks after inoculation (P = 0.01). (b) Proliferation scores increased shortly following challenge with GU strain B128 (filled symbols) and were significantly higher at all time points than either G1.1-infected (open symbols) or control animals (P < 0.001 for each).