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Identifying new antimicrobial agents against Mycobacterium tuberculosis

Pulmonary tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb), is a major global health concern, with roughly 8.7 million new cases diagnosed and 1.4 million deaths annually. Bactericidal agents are urgently needed for the treatment of Mtb because bacteriostatic drugs are not effective towards slowly replicating or dormant Mtb and this organism has developed resistance to most know antibiotics. There is increasing interest in new therapeutic agents for replicating and non-replicating (NR) Mtb. A novel assay developed in our lab utilizes an intracellular enzyme, Adenylate Kinase as a reporter of bacterial cell death. Dead bacteria lose cell wall integrity and release AK into the medium while live bacteria release little or no AK. Unlike most assays for antibacterial molecules the AK assay is not dependent on growth. Therefore, it will be directly applicable to dormant Mtb cells.

The goal of this research project is to identify putative new agents for the therapeutic intervention of Mtb. In the initial phase of this project, we will employ novel high through put screening campaigns to identify members of small molecule compound libraries that display antimicrobial activity toward this bacterial species.

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