迟缓爱德华氏菌与补体分子C3的相互作用及其对补体激活的影响

迟缓爱德华氏菌(Edwardsiella tarda)是海水养殖鱼类的重要病原菌。在前期研究中，申请人发现迟缓爱德华氏菌能够通过抑制补体旁路途径的激活而逃避血清补体的杀伤，发现迟缓爱德华氏菌能够与补体关键因子C3结合，但是其机制尚不清楚。在此前期研究的基础上，本项目拟利用免疫共沉淀、酵母双杂交、基因敲除等方法，深入研究迟缓爱德华氏菌与C3的相互作用机制，包括鉴定与C3相互作用的迟缓爱德华氏菌蛋白（命名为C3靶蛋白），阐明C3靶蛋白与C3的相互作用方式，揭示C3靶蛋白对补体激活的影响，确定迟缓爱德华氏菌抑制C3及补体系统激活的机制。本项目研究结果将加深我们对迟缓爱德华氏菌抗血清补体杀伤机制的了解，并为鱼类迟缓爱德华氏菌病的免疫防控提供理论指导。

Edwardsiella tarda is a severe pathogen to a wide range of economically important fish species. Recently, we have found that E. tarda circumvents serum attack by inhibiting complement activation via the alternative pathway, resulting in a high bacterial survival rate in fish serum; complement factor 3 (C3) can bind to E. tarda, but the mechanism remains to be discovered. Based on these observations, we will study the mechanism of E. tarda interaction with C3 by using methods such as CO-IP, yeast two hybrid and gene knockout. We will identify the target proteins (named C3 target proteins) of E. tarda that interact with C3 and examine the function of C3 target proteins on complement activation and on the virulence of E. tarda. We will analyze the mechanism of how E. tarda inhibits complement activation through the C3 target proteins. Our results will deepen our understanding of the serum-resistance mechanism of E. tarda and provide guidance for the prevention and control of edwardsiellasis in fish.