Modulation of Host Cell Function by Coxiella Burnetii

描述（由申请方提供）：贝氏柯克斯体是一种引起人类Q热的细胞内病原体。这种细菌病原体利用人类细胞的机制仍然未知。该项目的重点是确定柯克斯体中的关键毒力决定因素，并确定这些因素如何促进感染。Coxiella Dot/Icm系统是一种功能性蛋白分泌机器，通过将细菌效应物递送到宿主细胞中来促进感染。我们已经确定了柯克斯体的效应蛋白和宿主蛋白的重要感染。为了理解这些细菌决定簇和宿主蛋白之间的界面，将完成以下具体目标。目的1）利用全基因组筛选方法鉴定柯克斯体感染所需的效应子和宿主因子。目的2）确定Coxiella Dot/Icm系统在感染过程中的作用，并鉴定细胞内复制所需的细菌决定簇。目的3）阐明柯克斯体效应子的功能。

DESCRIPTION (provided by applicant): Coxiella burnetii is an intracellular pathogen that causes the human disease Q-fever. Mechanisms by which this bacterial pathogen exploits human cells remain unknown. This project is focused on identifying key virulence determinants in Coxiella and determining how these factors promote infection. The Coxiella Dot/Icm system is a functional protein secretion machine that promotes infection by delivering bacterial effectors into host cells. We have identified Coxiella effector proteins and host proteins important for infection. To understand the interface between these bacterial determinants and host proteins the following specific aims will be completed. Aim 1) Identify Coxiella effectors and host factors required for infection using genome-wide screening approaches. Aim 2) Determine the role of the Coxiella Dot/Icm system during infection and identify bacterial determinants required for intracellular replication. Aim 3) Elucidate the function of Coxiella effectors.