The structural and functional basis of reprogramming of vesicular transport by Salmonella enterica effector proteins

肠道沙门氏菌是一种兼性细胞内病原体，其在宿主细胞的膜结合区室（所谓的“含沙门氏菌的空泡”或SCV）内驻留和复制。沙门氏菌胞内部署由沙门氏菌致病岛2（SPI 2）编码的III型分泌系统（T3 SS）来操纵宿主细胞功能并实现胞内增殖。该项目应导致这些操作的分子基础的理解。我们的目标是i）定义单个SPI 2-T3 SS效应物在细胞转运的修饰和内体系统的重塑中的作用，ii）表征沙门氏菌内体系统重塑中涉及的宿主因子，iii）通过遗传筛选和蛋白质相互作用分析鉴定效应物的相互作用伴侣，以及最终iv）确定SPI 2-T3 SS效应物的结构/功能关系。在拟议的项目中的效应/靶相互作用的识别和分析将导致一个重要的细胞内病原体的细胞内策略的分子理解。

Salmonella enterica is a facultative intracellular pathogen that resides and replicates within a membrane-bound compartment of host cells, the so-called ‘Salmonella-containing vacuole’ or SCV. Intracellular Salmonella deploy a type III secretion system (T3SS) encoded by Salmonella Pathogenicity Island 2 (SPI2) to manipulate host cell functions and to achieve intracellular proliferation. The project should lead to the understanding of molecular basis of these manipulations. We aim to i) define the role of individual SPI2-T3SS effectors in modification of cellular transport and remodeling of the endosomal system, ii) characterize host factors involved in remodeling of the endosomal system by Salmonella, iii) identify interaction partners of effectors by genetic screens and protein interaction analyses, and ultimately iv) to determine the structure/function relationship of SPI2-T3SS effectors. The identification and analyses of effector/target interactions in the proposed project will lead to a molecular understanding of the intracellular strategies of an important intracellular pathogen.