金黄色葡萄球菌是一种致死性病原菌，人感染后能引起多种疾病甚至死亡。因抗生素滥用导致耐药菌株的大量出现和蔓延，使其成为威胁人类健康的重要因素。金黄色葡萄球菌分泌的类超抗原蛋白家族是一类强大的蛋白质武器，可攻击宿主免疫系统、凝血系统，在细菌侵染过程中发挥重要作用。尽管部分类超抗原识别的宿主因子及其功能已有报道，但大部分类超抗原的结构、宿主识别因子和功能仍不清楚。本项目将以金黄色葡萄球菌类超抗原蛋白为研究对象，测定2-3个类超抗原蛋白结构，鉴定宿主中未被发现的类超抗原蛋白相互作用因子，测定1-2个类超抗原蛋白与宿主因子的复合物结构，结合生物化学、细胞生物学等研究手段，阐释金黄色葡萄球菌类超抗原蛋白在宿主感染过程中发挥作用的分子机制, 筛选针对类超抗原蛋白的小分子抑制剂，为研发新型抗菌药物提供科学依据，并发表1-2篇高水平SCI论文。

Staphylococcus aureus is a lethal pathogen, which causes a wide range of infections and diseases. Because of the abuse of antibiotics, drug-resistant strains of S. aureus have emerged and spread in recent years and human health are threatened. A number of Staphylococcal superantigen-like proteins (SSLs, including SSL1-14) are secreted by S. aureus and function as protein weapons to attack human immune system and coagulation system, playing important roles in S. aureus infections. Target proteins of some SSLs have been identified, however, the counterparts of other SSLs and their functions remain to be characterized. We will study the structures and functions of S. aureus SSLs and determine the structures of 2-3 SSLs members. We will identify new counterparts of SSLs and determine 1-2 structures of SSL-counterpart complexes. We will analyze the interactions between the S. aureus SSLs and their counterparts, together with other biochemical and cell biological approaches, study the molecular mechanisms of SSLs in S. aureus infections. The inhibitors of SSLs will be screened and designed based on the determined structures and biochemical studies, so that the antimicrobial drugs will be explored. Based on our studies, we will publish 1-2 SCI papers in high-profile journals.