Ess系统新分泌蛋白EsxX在社区获得性金葡菌流行株ST398致病中的作用及机制

已报道的金葡菌Ess分泌系统两个WXG家族分泌蛋白EsxA和EsxB在细菌致病中发挥重要作用。课题组前期在高毒力社区获得性金葡菌流行株ST398 Ess分泌系统中发现第三个结构和序列全新的WXG家族分泌蛋白，命名为EsxX。该分泌蛋白在高毒力株ST398致病中扮演重要角色。为详尽阐明这一新分泌蛋白在ST398致病中的作用及具体分子机制，课题组拟通过构建ST398 Ess分泌系统各基因突变株及互补表达株、获得Ess分泌系统各蛋白及多克隆抗体基础上，从体外和体内角度明确课题组新发现的Ess分泌系统WXG家族蛋白EsxX具体分泌机制及与其他分泌蛋白之间的关系，EsxX分泌的表达调控机制及促进宿主细胞裂解和炎症反应具体分子机制。研究成果为补充完善金葡菌Ess分泌系统蛋白结构和功能、为社区获得性金葡菌高毒力具体分子机制提供新的理论依据。最终为及时诊断与感控措施实施及设计新的抗感染药物或疫苗提供药靶。

S. aureus encodes the specialized ESAT-6 Secretion System (ESS). EsxA and EsxB secreted by ESS, belong to the WXG family proteins, are required for the pathogenesis of S. aureus infections. Our group found the third secreted proteins of the WXG family in the ESS of highly virulent community acquired epidemic S. aureus (CA-SA) clone ST398, we named it EsxX. EsxX is only found in high toxicity CA-SA ST398, and plays an important role in bacterial pathogenesis. To elucidate the role of this novel secreted protein EsxX in the pathogenesis of CA-SA ST398 and its pathogenic mechanism, our group will construct the mutant strains and complementary expression strains of CA-SA ST398 ESAT-6 Secretion System, obtain the proteins and polyclonal antibodies of ESAT-6 Secretion System, and then from in vitro and in vivo experiments to clarify the specific secretory mechanism of this novel WXG family secreted protein EsxX and the relationship with other secreted proteins in ESS, the expression regulation mechanism of EsxX secreted protein and the specific molecular mechanisms for the promotion of host cell lysis and inflammation. Our results will provide more information about the structure and function of the ESAT-6 Secretion System of S.aureus, and also provide new evidence for the specific molecular mechanism of high virulence of community acquired S.aureus. The results will provide ideas for timely diagnosis, implementation of the control measures and provide drug target for design new anti infective drugs or vaccines.