铜绿假单胞菌III型分泌系统杀白色念珠菌机制研究

铜绿假单胞菌和白色念珠菌的跨界相互作用是近年来研究的热点之一，然而机制研究相对滞后，尤其在绿假单胞菌III型分泌系统（T3SS）杀白色念珠菌功能和机制的揭示方面还一片空白。本项目针对当前“铜绿假单胞菌如何感知白色念珠菌的存在以及如何调控T3SS做出反应的”这一基本科学问题，以铜绿假单胞菌和白色念珠菌为研究对象，在前期发现铜绿假单胞菌T3SS具有杀死白色念珠菌功能的基础上，分别从效应蛋白、营养条件和生物膜三方面深入揭示其分子机制，同时从信号分子入手，借助T3SS启动子报告系统，通过受体鉴定、信号通路分析和调控蛋白筛选构建信号跨界调控网络，最终通过细菌-真菌宿主体内互作和效应蛋白广谱抗真菌研究阐明铜绿假单胞菌T3SS杀真菌的生理学意义。本项目的研究是对T3SS功能认识的强化和铜绿假单胞菌-白色念珠菌相互作用领域的补充，具有重大的生理生态学意义和潜在的应用前景。

Although the cross-kingdom interaction between Pseudomonas aeruginosa and Candida albicans is one of the current research hotspots, the mechanism research is lagging behind. In particular, there has no report in revealing the function and mechanism on P. aeruginosa type III secretion system (T3SS) kills C. albicans until now. In this project we aim to reveal the mechanisms on how does P. aeruginosa recognize the presence of C. albicans and how to regulate T3SS to make respond, which is a current basic scientific problem in this field. Based on the previous discovery that the P. aeruginosa T3SS mediates its killing of C. albicans, we will further reveal its molecular mechanism from three aspects of effectors, nutritional conditions and biofilm formation respectively by using P. aeruginosa and C. albicans as the materials. In addition, we will start with quorum sensing signal, with the help of T3SS promoter reporter system, to construct the signal cross-kingdom interaction network through receptor identification, signal pathway analysis and regulatory protein screening. And finally clarifying the physiological significance of P. aeruginosa T3SS in killing C. albicans through determining the in vivo interaction of bacteria-fungal in host and the broad-spectrum antifungal ability of effectors. Through the implementation of this project, it will not only broaden our understanding of T3SS function and complement the field of P. aeruginosa-C. albicans interaction research, but also has great physiological ecology significance and potential application prospects.