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

D Israel

N Salama

C Arnold

S Moss

M Blaser+2 authors

^{Division of Gastroenterology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA}^{Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, USA}^{Division of Gastroenterology, Rhode Island Hospital, Brown University School of Medicine, Providence, Rhode Island, USA}^{Division of Infectious Diseases, and}^{Department of Pathology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA}^{Department of Veterans Affairs Medical Center, Nashville, Tennessee, USA}

Address correspondence to: Richard M. Peek, Jr., Division of Gastroenterology, Vanderbilt University School of Medicine, C-2104 Medical Center North, Nashville, Tennessee 37232-2279, USA. Phone: (615) 322-5200; Fax: (615) 343-6229; E-mail: ude.tlibrednav.liamcm@keep.drahcir.

Received 2000 Sep 29; Accepted 2001 Jan 29.

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.

Abstract

Acknowledgments

Supported in part by the NIH (KO8 DK02381, R29 CA77955, R01 DK50837, and RO1 AI38459), and by the Medical Research Service of the Department of Veterans Affairs. We thank Tyler Richmond and Uma Krishna for excellent technical assistance.

Acknowledgments

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