生物被膜的形成阻碍了抗生素及免疫系统对金黄色葡萄球菌的快速清除，延长了临床治疗周期，增大了形成耐药菌株的风险。抑制生物被膜的形成可以有效提高金葡菌感染的治疗效率，但现有生物被膜驱散药物及治疗策略存在诸多缺陷，无法在临床上广泛使用。近年来，申请人一直致力于揭示金葡菌关键生理过程的结构生物学基础，并希望由此找到可以有效控制金葡菌感染和增殖的潜在药物设计靶点。在本项目中，申请人拟综合运用结构生物学、生物化学和细胞生物学技术手段，解析金葡菌生物被膜形成关键调控因子SarX蛋白与agr转录系统及ica转录系统间各自的复合物三维结构，阐明其促进金葡菌生物被膜形成的分子机制；此外，我们还希望通过所获得的结合表面结构信息及DNA别构信息，发现能抑制金葡菌生物被膜形成的潜在药物设计靶点。上述研究工作的开展将为金黄色葡萄球菌生物被膜阻断剂的研究开发提供重要线索，为从转录水平阻止生物被膜的形成提供新的思路。

Biofilm formation gives Staphylococcus aureus temporary resistant to antibiotics, and also helps it to evade from the immune system of patient. S. aureus biofilm-associated infections are difficult to treat with antibiotics and are becoming a very troublesome clinical type of disease. Biofilm dispersal has been largely concerned as a potential means of treating S. aureus biofilm-associated infections. However, present dispersal agents and the therapeutic strategy for S. aureus biofilm meet large challenges before being used in the clinic treatment. In this project, we plan to solve the 3D structure of the biofilm formation transcription regulator SarX with both of agr and ica systems and illuminate the mechanism of how SarX facilitates the biofilm formation in S. aureus. We also expect to find the potential novel rational therapeutic target for biofilm-associated infection treatment.