Helicobacter pylori cag-type IV secretion system facilitates corpus colonization to induce precancerous conditions in mongolian gerbils

Gabriele Rieder, Juanita L. Merchant, Rainer Haas

Research output: Contribution to journalArticlepeer-review

152 Scopus citations


Background & Aims: Epidemiological studies suggest that atrophic corpus-dominant gastritis is an increased risk factor for gastric carcinogenesis. The role of the Helicobacter pylori type IV secretion system (T4SS) for pathogenesis in the Mongolian gerbil model was explored. Methods: Mongolian gerbils were infected for 32 weeks either with H pylori type I strain B128 or with isogenic mutant strain B128Δ cytotoxin-associated gene (cagY) or B128ΔcagA, defective in T4SS or in the production of its effector protein CagA, respectively. Quantitative H pylori reisolation was performed from the gastric antrum and corpus separately, cytokines were measured by quantitative reverse-transcription polymerase chain reaction, and gastric pH and hormones were determined. Results: B128-infected gerbils harbored high numbers of bacteria in the gastric antrum and corpus, whereas B128ΔcagY and B128ΔcagA colonized the antrum more densely than the corpus. All infected animals showed a strong antral inflammation and epithelial cell proliferation. B128-infected, rather than mutant-infected, gerbils presented a severe transmural inflammation with huge lymph aggregates, increased proliferation, significant atrophy, and mucous gland metaplasia in the corpus. Plasma gastrin levels and gastric pH values were significantly increased only in B128-infected gerbils. In all infected animals, the expression of the proinflammatory cytokines interleukin 1β, interferon γ, and growth-regulated protein was considerably increased in the antrum, but only in wild type-infected animals was an increase seen in the corpus mucosa. Conclusions: The presence of an intact T4SS allows H pylori to colonize the gastric corpus. This results in atrophic corpus-dominant gastritis, a severe precancerous condition, thus highlighting T4SS and CagA as major risk factors for gastric cancer development.

Original languageEnglish (US)
Pages (from-to)1229-1242
Number of pages14
Issue number5
StatePublished - May 2005
Externally publishedYes

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology


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