细菌VI型分泌系统的非接触杀菌新功能研究

新型细菌分泌系统T6SS是当前微生物领域一个新的研究热点，其作为接触依赖型细菌竞争武器的观点已被广泛接受。我们的前期研究首次发现T6SS还能以非接触依赖的方式，在靶细胞受体蛋白介导下杀菌。本项目将在这一原创新发现的基础上，进一步使用不同方法夯实T6SS的非接触杀菌功能，鉴定介导T6SS非接触依赖杀菌功能的新型毒素蛋白的酶学活性和毒性机制，筛选鉴定毒素蛋白的靶细胞受体蛋白，揭示其进入靶细胞的途径和机制，阐明靶细胞受体蛋白在介导非接触依赖T6SS杀菌中的功能，并研究非接触依赖型T6SS杀菌在肠道细菌定殖、生物膜形成、致病性和对肠道微生物组结构影响等方面的功能，从而深入揭示非接触依赖型T6SS杀菌的作用机制和生理生态意义，以拓展当前学术界对T6SS及其效应蛋白功能的认识，完善现有关于毒素蛋白靶向细胞途径的认知，并为开发T6SS塑造微生物群落结构、维持微生态稳定的工具属性奠定基础。

It has been widely accepted that the recently discovered bacterial secretion system, Type VI secretion system (T6SS), is adopted by a wide variety of species as an efficient weapon for inter-bacterial competition through a contact-dependent manner. However, we recent discovered that T6SS can also achieve their killing function in a contact-independent manner. Standing on the foundation of this breakthrough discovery, in this project we will further confirm this novel killing mode, identify the enzymatic activities of the toxic effectors that mediate the contact-independent killing, screen and identify membrane receptors on the target bacterial cell recognized by these toxic effectors, thus deciphering the mechanisms of the contact-independent killing and the pathways involved in the entrance of toxin effectors into the target bacterial cells. The project will also elucidate the effects of the T6SS contact-independent killing on biofilm formation, pathogenicity and microbial community structure in animal models, thus revealing the physiological and ecological significance of the T6SS contact-independent killing. The completion of this project will not only expand the current understanding of T6SS and its effectors, but improve the existing knowledge for the pathways of toxic effectors entering into the target bacterial cells. It will also lay the foundation for the development of T6SS as a future ecological tool in modifying microbial community structure and maintaining microecology balance.