白念珠菌是重要的机会致病真菌，位居全身性感染死亡原因第4位。白念珠菌与金黄色葡萄球菌共感染环境下，微生物相互作用在其共生状态和疾病的发生发展中至关重要。前期工作发现金黄色葡萄球菌分泌的ClpP蛋白酶(SaClpP)对白念珠菌菌丝发育存在抑制作用并降低白念珠菌对真菌药物的最低抑菌浓度，但其关键的信号通路和调控机制尚不明晰。本项目拟开展如下研究：1）利用LC-MS、RNA-Seq、Co-IP、ChIP等方法研究SaClpP影响白念珠菌形态转换的底物、信号通路和调控分子基础；2）应用体内外药敏试验、ROS、脂质过氧化、线粒体膜电压检测等技术，分析SaClpP对白念珠菌药物敏感性的影响及其分子机制；3）通过免疫组化染色等方法研究小鼠模型中，SaClpP影响宿主免疫反应进而参与炎症的致病机制。以期阐明金黄色葡萄球菌重要毒力因子调控白念珠菌致病性和药物敏感性的分子机制，为复杂感染防控提供新靶点和策略。

Candida albicans is an important opportunistic fungus, is the fourth leading cause of death from systemic infection. In the co-infection environment of Candida albicans and Staphylococcus aureus, microbial interactions are essential in the development of microbial symbiosis and diseases. Our preliminary data showed that S. aureus casein lyase proteinase P (SaClpP) inhibited the mycelial development of C. albicans and reduced the minimum inhibitory concentration of antifungal agents against C.albicans, but the underlying mechanisms are unclear. This project is aimed to carry out the following research: first, we will use LC-MS, RNA-Seq, Co-IP and ChIP to identify the substrate and signaling pathway of SaClpP in regulating C. albicans mycelial development. Second, we will analyze the effect and molecular mechanism of SaClpP on the drug sensitivity of C. albicans using in vitro and in vivo assays. Third, we will investigate the role of SaClpP in host immune response caused by C. albicans infection. Our goal is to explore the molecular mechanisms of C. albicans pathogenicity and drug sensitivity during interaction with S. aureus. The information derived from this application will help us determine new potential targets and strategies for complicated infection prevention and control.