Identification and validation of novel virulence factors of Helicobacter pylori

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First, we sought to confirm previously reported virulence factors, especially cagPAI. We compared anti-CagA antibody seropositivity between gastric cancer patients and matched controls by using recombinant CagA (a product of cagPAI) and found that anti-CagA positivity was associated with an odds ratio of 10 concerning gastric cancer. We also validated virulence of cagPAI in Mongolian gerbils using cagPAI gene knocked out mutants, showing that inflammation and tumorogenesis require cagPAI.Next, we investigated H. pylori-mediated induction of intracellular signaling pathways and demonstrated activation of NF-kappa B through IKK and TRAFs ; of SRE and AP-1 through the ERK cascade ; and of cyclin D1 through the MAPK cascade. The presence of cagPAI and direct contact between bacteria and host cells were required in the induction of those intracellular signals. We applied cDNA microarray analysis to examine various gene expressions in the host cells.Finally, we established a short-term Mongolian gerbil infection model to validate H. pylori virulence factors in vivo.