Identification of M. tuberculosis Lipid Kinases

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.