Transcription of H. pylori Genes in the Rhesus Monkey

Project: Research project

Project Details

Description

DESCRIPTION (provided by the applicant): Helicobacter pylori is an extremely common infection that causes gastritis and is clearly implicated in the development of peptic ulcer disease and gastric cancer. A full understanding of H. pylori pathogenesis requires an analysis of bacterial gene expression in vivo in a relevant animal model. The availability of the complete H. pylori genome sequence, together with novel technologies for measurement of gene expression, makes it possible to address this problem in the rhesus monkey model that we have recently developed at the California Regional Primate Research Center (CRPRC). We hypothesize that H. pylori genes important in virulence will be induced by contact with the host gastric epithelium. Furthermore, we propose that bacterial gene expression in the host will be modulated by the presence of the cagA pathogenicity island and by luxS, a gene implicated in quorum sensing. Specific pathogen free rhesus monkeys will be inoculated with wild type H. pylori or with isogenic mutants carrying deletions in the cagA pathogenicity island or in luxS. In vivo transcription in targeted genes will be measured by quantitative RT-PCR during a 6-month period of infection. The results in animals infected with wild type and mutant strains will be compared over time. Furthermore, we will compare changes in gene transcription between cells grown in vitro and those isolated in vivo. An understanding of the dynamic interaction between host and pathogen may point the way toward critical proteins that may be useful as targets for therapy or vaccine development.
StatusFinished
Effective start/end date5/20/015/31/04

Funding

  • National Institutes of Health: $146,233.00
  • National Institutes of Health: $145,677.00

ASJC

  • Medicine(all)

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