沙门氏菌外膜蛋白MipA的功能研究

Salmonella is one of the most common human pathogenic bacteria and has seriously affected people's health. Based on the preliminary result of our research group, mipA deletion mutant Salmonella Paratyphi A has the higher virulence than wild type , in this study, we will explore further the function of this outer membrane protein in the following proposed ways: 1) to evaluate the adhesion and invasion ability to epithelial cells of mipA mutant as well as its survival and reproduction ability in macrophages; 2) to evaluate the regulation of MipA to transcription of bacterial genome, in particular those for known virulence factors, through comparative transcriptomics analysis ; 3) to evaluate the influence of mipA deletion on proteomic profile of the bacteria through comparative proteomics analysis, to indentify the altered virulence factors; 4) to verify whether the function of mipA is universal in Salmonelleae, by constructing a Salmonella Typhimurium mipA deletion mutant and evaluating its virulence. With these studies, we hope to clarify the mechanism for the pathogenesis of Salmonella. Provided that the antagonistic effect of MipA on Salmonella's virulence has been confirmed meanwhile this effect proved to be universal in Salmonelleae, the finding will be of extraordinary significance for the prediction of new Salmonella virulent strain and the further demonstration of the relationship between the genetic variation of pathogenic bacteria and its pathogenicity.

沙门氏菌（Salmonella）是常见的人类致病菌，严重影响人们的健康。本课题组在前期研究中发现甲型副伤寒沙门氏菌mipA缺失突变株较野生株有毒力增强的现象，本课题拟从以下方面深入探讨该外膜蛋白的功能：1) MipA突变体粘附、侵袭肠上皮细胞能力以及在巨噬细胞中生存和繁殖能力的评价；2）通过比较转录组学技术分析mipA基因对细菌基因组转录的调控，尤其是已知毒力因子的调控；3）利用比较蛋白质组学技术分析mipA基因缺失对细菌蛋白质组的影响，寻找发生变化的毒力因子；4) 通过构建鼠伤寒沙门菌mipA缺失突变株并对其进行毒力评价，考察MipA的功能在沙门氏菌属中是否具有普遍性。通过上述研究，希望进一步解析沙门氏菌的致病机理。一旦MipA对毒力的拮抗作用被证实且在沙门氏菌中具有普遍意义，对于预测新毒株的出现以及进一步阐述病原菌遗传变异与致病的关系具有非凡的意义。