马链球菌兽疫亚种(SEZ)是引起我国猪链球菌病的重要病原之一，人食用被该菌污染的食物或是与患病动物有过密切接触亦会感染。本实验室在SEZ ATCC35246的基因组上发现该菌株特有的Fic结构域蛋白基因ficSEZ，该基因与细菌毒力的关系以及在细菌感染过程中的作用机理等问题均有待阐明。本项目拟构建ficSEZ基因缺失株，以小鼠为动物模型，分析其与毒力的关系；利用bEnd.3细胞模型研究该蛋白对细胞骨架以及细胞信号通路的影响；探索FicSEZ的腺苷酰化等功能以及对应的抗毒素蛋白Anti-FicSEZ对其功能的影响；采用酵母双杂交技术尝试从分子层面找出宿主中与FicSEZ蛋白有互作的靶蛋白，结合信号通路芯片结果，发掘FicSEZ蛋白影响细菌毒力的其他可能机制。本研究可以帮助阐明FicSEZ蛋白在ATCC35246感染中的作用机制，亦对其他动物病原菌的相关研究有借鉴意义。

Streptococcus equi ssp. zooepidemicus (SEZ) is the major cause of Swine Streptococcosis in China. It can infect humans via zoonotic transmission from domesticated animals and cause invasive infections in humans. We sequenced and analyzed the whole genome of S. zooepidemicus ATCC35246, found a unique Fic domain protein gene ficSEZ, this kind of genes are always related to bacterial virulence. Thus, this study attempts to analyze, express and purify FicSEZ protein, detected their adenylylation on Rho GTPase family proteins; construct the ficSEZ knock out strains and analyze the pathogenicity and tissue distribution in mice; Analysis of cytotoxicity and signal pathway are based on bEnd.3 cell model; Explore the influence of Anti-FicSEZ on the function of FicSEZ; Yeast Two Hybrid and some other protein-protein interaction technologies are taken to detect the proteins which can interact with FicSEZ during ATCC35246 infection, by combining the results of Microarray, it will then be possible to discover some new mechanism of FicSEZ influence bacterial virulence. This research will increase our knowledge about the mechanism of FicSEZ in ATCC35246 infection and contribute to the prevention and control of Swine Streptococcosis in China.