Mycobacterium tuberculosis Counter-immune MechanismsThe bacterial pathogen Mycobacterium tuberculosis (Mtb) is unusual in its ability to persist in the lungs of infected humans for many years, despite triggering a robust immune response. My laboratory seeks to identify and characterize factors that Mtb requires for evasion of host adaptive immunity and persistence. We use a combination of bacterial genetics and the mouse infection model to identify these "counter-immune" factors.The laboratory is currently focused on characterization of an Mtb signal transduction system, Pst/SenX3-RegX3, which regulates gene expression in response to phosphate availability. Mtb mutants that lack components of this system are specifically sensitive to host adaptive immunity and fail to persist in the lungs of mice. We aim to identify the genes controlled by this system that directly contribute to avoidance of host immune responses. Knowledge of these interactions between host and pathogen may contribute to vaccine design, as well as provide novel targets for therapeutic intervention.
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