Virulence Factors of Helicobacter pylori Responsible for Gastric Diseases in Mongolian Gerbil

doi:10.1084/jem.192.11.1601

Published online 4 December 2000.

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© The Rockefeller University Press, 0022-1007/2000/12/1601/ $5.00
The Journal of Experimental Medicine, Volume 192, Number 11, December 4, 2000 1601-1610

Original Article

Virulence Factors of Helicobacter pylori Responsible for Gastric Diseases in Mongolian Gerbil

Keiji Ogura^a,b, Shin Maeda^a, Masafumi Nakao^c, Takeshi Watanabe^c, Mayumi Tada^c, Toshimasa Kyutoku^c, Haruhiko Yoshida^a, Yasushi Shiratori^a, and Masao Omata^a
^a Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655, Japan
^b Division of Gastroenterology, The Institute for Adult Diseases, Asahi Life Foundation, Tokyo 160-0023, Japan
^c Pharmaceutical Research Division, Takeda Chemical Industries, Limited, Osaka 532-8686, Japan

Correspondence to: Keiji Ogura, Dept. of Gastroenterology, University of Tokyo, Hongo 7-3-1, Bunkyo, Tokyo 113-8655, Japan. Tel:81-3-3815-5411 Fax:81-3-3814-0021 E-mail:OGURA-2IM{at}h.u-tokyo.ac.jp.

Helicobacter pylori infection induces various gastroduodenaldiseases. We examined the role of two genes, vacA and cagE,in the gastric pathogenesis induced by H. pylori using a long-term(62 wk) animal model. Reportedly, both genes are associatedwith the virulence of H. pylori: vacA encodes vacuolating cytotoxin,and cagE, with other genes in the cag pathogenicity islands,encodes a type IV secretion system. Mongolian gerbils were challengedin this study by a wild-type TN2 strain and its isogenic mutantsof cagE or vacA. The wild-type and vacA mutants induced severegastritis, whereas cagE mutants induced far milder changes.Gastric ulcer was induced at the highest rate (22/23) by thewild-type TN2, followed by the vacA mutant (19/28). No ulcerwas found in the gerbils infected with the cagE mutant (0/27)or in controls (0/27). Intestinal metaplasia was also foundin the gerbils infected with the wild-type (14/23) or vacA mutant(15/28). Gastric cancer developed in one gerbil with wild-typeinfection and in one with vacA mutant infection. In conclusion,the knocking out of the cagE gene deprived wild-type H. pyloriof the pathogenicity for gastritis and gastric ulcer, suggestingthat the secretion system encoded by cag pathogenicity islandgenes plays an essential role.

Key Words: gastritis, inflammation, mutagenesis, pathogenicity, animalexperiments

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