Identification and validation of novel virulence factors of Helicobacter pylori

首先，我们试图确认之前报道的毒力因子，尤其是 cagPAI。我们使用重组CagA（cagPAI的产品）比较了胃癌患者和匹配对照之间的抗CagA抗体血清阳性，发现抗CagA阳性与胃癌的比值比为10相关。我们还使用 cagPAI 基因敲除突变体验证了 cagPAI 在蒙古沙鼠中的毒力，表明炎症和肿瘤发生需要 cagPAI。接下来，我们研究了幽门螺杆菌介导的细胞内信号通路诱导，并证明通过 IKK 和 TRAF 激活 NF-kappa B； SRE 和 AP-1 通过 ERK 级联；以及通过 MAPK 级联的细胞周期蛋白 D1。诱导这些细胞内信号需要 cagPAI 的存在以及细菌和宿主细胞之间的直接接触。我们应用cDNA微阵列分析来检测宿主细胞中的各种基因表达。最后，我们建立了短期蒙古沙鼠感染模型来验证幽门螺杆菌体内毒力因子。

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.