奎尼酸靶向细胞分裂关键蛋白FtsZ抑制金黄色葡萄球菌作用的分子机制研究

金黄色葡萄球菌是一种常见的食源性病原菌，控制食品中金葡菌的污染、开发安全高效的抑菌剂对保障食品安全具有重要意义。细胞分裂蛋白FtsZ在原核细胞的结构和功能上具有高度保守的特性，对细胞分裂至关重要，因此FtsZ是新一代抑菌剂的理想靶标。申请人前期研究发现奎尼酸能抑制金葡菌细胞分裂隔膜形成、导致隔膜位置偏离，并上调基因ftsZ表达，与蛋白FtsZ发生相互作用，提示奎尼酸可能通过靶向FtsZ抑制金葡菌生长。鉴于目前FtsZ抑制剂作用机理研究的局限性，本项目拟采用表面等离子体共振、免疫共沉淀、全内反射荧光显微镜等技术，探究奎尼酸对金葡菌FtsZ生物功能的动态影响；明晰奎尼酸与蛋白FtsZ相互作用的动力学模式；研究奎尼酸对细胞分裂蛋白FtsZ及其下游蛋白互作网络的动态影响。本项目的实施将阐明奎尼酸靶向细胞分裂关键蛋白FtsZ抑制金葡菌作用的分子机制，为奎尼酸的应用和FtsZ抑制剂的开发提供理论基础。

Staphylococcus aureus is an important foodborne pathogen. It is of great significant for food safety to control the S.aureus contamination and develop safe and efficient antibacterial agents. FtsZ is structurally and functionally conserved across bacteria, and plays a specific role in bacterial cell division, which revealed that FtsZ is a novel target for antibacterial agents. Previously, we have demonstrated that quinic acid could disturb the position and formation of septum, up-regulate the expression of the gene ftsZ, and interact with protein FtsZ. These results implied that quinic acid probably inhibit S.aureus by targeting the critical protein FtsZ. However, the study on the molecular mechanism of FtsZ inhibitor was limited. Therefore, we will combine the surface plasmon resonance, co-immunoprecipitation, and total internal reflection fluorescence to dynamically monitor the effect of quinic acid on the biological function of FtsZ, to clarify the relative interaction mode and binding kinetic parameters between quinic acid and FtsZ, and to assess the effect of quinic acid on FtsZ and its downstream protein interaction network. This project will elucidate the molecular mechanism for the inhibitory action of quinic acid on S.aureus by targeting the critical protein FtsZ of cell division, together with providing a theoretical basis for the application of quinic acid and the development of FtsZ inhibitors.