Identification of M. tuberculosis Lipid Kinases

描述(申请人提供)：结核病感染了大约三分之一的世界人口，是一个全球卫生问题。致病分支杆菌阻止吞噬小体成熟并在宿主巨噬细胞内建立细胞内生态位的能力是感染的一个标志。这种情况发生的机制还不是很清楚。据推测，结核分枝杆菌主动分泌与抑制吞噬小体成熟有关的效应物。这些因子可能是蛋白质或脂肪蛋白，它们将被传递到吞噬体腔，在那里它们可以靶向并调节正常的宿主信号和细胞内运输。该项目的目标是识别结核分枝杆菌效应蛋白激酶。这项建议的具体目的是：1.鉴定结核分枝杆菌分泌的与结核分枝杆菌液泡相关的ATP水解酶。2.检测重组效应蛋白对宿主细胞的活性。

DESCRIPTION (provided by applicant): Tuberculosis infects roughly one third of the world population and is a global health concern. The ability of pathogenic mycobacteria to arrest phagosome maturation and establish an intracellular niche within the host macrophage is a hallmark of the infection. The mechanism by which this occurs is not well understood. It is hypothesized that M. tuberculosis actively secretes effectors involved in the arrest of phagosome maturation. Such factors could be protein or lipid kinases that would be delivered to the phagosome lumen where they could target and modulate normal host signaling and intracellular trafficking. The goal of this project is to identify M. tuberculosis effector kinases. The specific aims of this proposal are: 1. The identification of ATP-hydrolyzing enzymes secreted by M. tuberculosis and associated with the M. tuberculosis vacuole. 2. Assessing the activity of recombinant effector proteins on the host cell.