毒力因子spvD在调控NF-kB通路致肠炎沙门菌全身感染中的作用机制研究

肠炎沙门菌是沙门氏菌中导致人类腹泻的主要血清型，但是其所致的全身感染日渐成为严重的临床挑战。申请人通过前期的基因组学研究发现，spvD基因可能是肠炎沙门菌导致全身感染的重要毒力基因。近期有研究显示，鼠伤寒沙门菌中效应蛋白SpvD能够下调NF-kB信号通路，增强其在小鼠中的毒力。本课题经比对发现这两种血清型沙门菌中该效应蛋白在氨基酸序列154和161处有变异。基于此，本课题首先利用体外细胞感染实验和小鼠感染模型验证spvD基因可能是肠炎沙门菌导致全身感染的重要毒力基因的这一假说；然后，申请人拟通过研究肠炎沙门菌spvD对NF-kB通路的影响来探索其导致全身感染的机制；最后，比对不同血清型沙门菌氨基酸差异对于通路调控以及全身感染能力的影响。

Salmonella enterica serovars Enteritidis (S. Enteritidis) is a main serotype of Salmonella that commonly result in self-limiting diarrhoea. However, more and more cases that S. Enteritidis can invade normally sterile sites were found, and systemic infections caused by S. Enteritidis become a huge clinical challenge. Genomics comparison results strongly suggest that spvD is an important virulence factor leading to systemic infection. Some researches demonstrated that effector protein SpvD can negatively regulated the NF-κB signaling pathway and promote virulence of Salmonella enterica serovars Typhimurium (S. Typhimurium) in mice. And we found that the amino acid sequence of SpvD is highly conserved across these two different S. enterica serovars, except residue154 and 161. Based on these, our study first to verify the hypothesis that the spvD gene may be an important virulence gene for S. Enteritidis causing systemic infection by the in vitro experiment and animal experiment; second, this study intends to research the effect of spvD on NF-kB signaling pathway and to explore the mechanism of systemic infection; third, compare the effect of amino acid differences of two different serotypes of Salmonella on pathway regulation and whether it leads to differences in systemic infection.