兽医临床监测数据显示从表观健康猪扁桃体分离到的猪链球菌普遍编码VII型分泌系统（T7SS）。前期研究发现T7SS缺失株与野毒株相比丧失生长竞争优势，且显著诱导宿主细胞凋亡及NF-κB炎症应答上调。因此，解析T7SS功能将有助于阐明猪链球菌逃避宿主免疫清除的机制，为疾病防控提供理论参考。分析NCBI已有数据发现T7SS核心基因essC下游普遍编码LXG及MSE蛋白，且LXG携带9种潜在效应基序，而MSE有4种C端基序。项目将探明猪链球菌T7SS分子流行规律及上述效应子家族编码特性，拟运用基因缺失、免疫共沉淀、氨基酸点突变等技术鉴定上述效应子的潜在靶蛋白及活性作用位点，最终阐明LXG-Ex1靶向Caspase-3抑制宿主细胞凋亡，及MSE-Ex1/2/3靶向NF-κB逃避宿主炎症应答的分子机制。本研究将扩展对T7SS效应子家族及其致病作用的认知，为解析猪链球菌逃避宿主免疫清除的机制提供参考。

Veterinary clinical monitoring found that numerous Streptococcus suis (SS) strains could be isolated from tonsils of apparently healthy pigs, and which widely encoded type VII secretion system (T7SS) clusters. Recent studies of T7SS identified several novel effectors for interbacterial competition and full virulence, while similar research in SS lagged behind. Our preliminary study found that the inactivation of T7SS caused the loss of advantage in growth competition in SS, and significant induced the upregulation of host cell apoptosis and NF-κB related inflammatory response. Therefore, further determination of T7SS functions will help us to better clarify the underlying mechanism of SS colonization and escaping from host immune clearance, and to develop effective prevention strategies for diseaese control. In this proposed study, based on our preliminary analysis to published data at NCBI website, we found that LXG and MSE proteins were widely encoded at the downstream of essC gene in T7SS loci. Especially, 9 and 4 different C-terminal sequences were carried by these LXG and MSE proteins, respectively. Thus, our following work will try to clarify the molecular epidemiology and effector coding characteristics of T7SS in SS, and identified the host target proteins of T7SS effectors and their interaction key sites using the technologies in gene deletion, co-immunoprecipitation and amino acid point mutation. All these works will contribute to clarify the mechanisms that T7SS delivers LXG-Ex1 effector to hijack host Caspase-3 to disturb cell apoptosis, and delivers MSE-Ex1/2/3 to hijack NF-κB pathway to inhibit inflammatory response. This proposed study will further extend our knowledge to the identification of T7SS effector families and their pathogenic effect, and provide reference for the further exploration of the underlying mechanism in SS escaping from host immune clearance.