| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2000: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1999: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Research Abstract |
The cagA gene is part of a 40-kb DNA insertion that was considered to have typical features of a bacterial pathogenicity island (PAI). The cag PAI contains 31 genes, and six of the cag genes are thought to be encoded by a putative type IV secretion system specialized in the transfer of a variety of multimolecular complexes across the bacterial membrane to the extracellular space or into other cells. Recent studies indicated that CagA is delivered into the epithelial cells by the cag type IV secretion system, where it is phosphorylated on tyrosine residues and wired to eukaryotic signal transduction pathways and cytoskeletal plasticity. Chromosome walking and mutational experiments identified several genes that are needed for IL-8 induction. One of these genes is cagE, which is a homologue of the ptlF and virB4 genes of Bordetella pertussis and Agrobacterium tumefaciens respectively. The cagE gene is considered to construct the cag type IV secretion system. The aims of the present study
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were to clarify the association between the cagE gene and clinical outcome, to investigate the strain diversity of H.pylori, and to analyze the relationship between the cagE gene and two other virulence factors ; cagA and vacA, in two areas in Japan (Fukui and Okinawa) where the prevalence of duodenal ulcer and gastric cancer risk are quite different. Forty-two isolates from Fukui (13 from gastric ulcer, 14 from duodenal ulcer, and 15 from gastritis patients) and 39 from Okinawa (10 from gastric ulcer, 8 from duodenal ulcer, and 21 from gastritis patients) were subjected to analysis of the cagE gene by PCR and DNA sequencing. In addition, the cagA and vacA gene status were analysed by Southern analysis and DNA sequencing. Eighty of 81 isolates possessed the cagE gene and all isolates possessed the cagA gene. The vacA genotype s1c/m1 was a major genotype in both areas in Japan (Fukui 88.1% ; 37/42, Okinawa 74.4% ; 29/39). There was no significant association between cagE, cagA status, or vacA genotype and clinical outcome. Phylogenetic analysis of the cagE gene indicated that most Japanese isolates formed a different cluster from strains isolated in the West with an association with the vacA genotype. Less
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