Tuberculosis (TB), the systemic infection caused by the intracellularly surviving pathogenic microorganism Mycobacterium tuberculosis (Mtb), is a serious world health threat. The primary objective of this project is to investigate novel strategies to increase the sensitivity of both actively growing and dormant cells to chemotherapeutics and the host immune system by targeting components of the mycothiol-dependent detoxification system, namely mycoGlyoxalase-1 and mycothiol-S-transferase. The development of potent and selective chemical probes for these enzymes will allow us to dissect the endogenous role of these key enzymes in the intracellular survival of the TB pathogen.
Rawat, M.; Av-Gay, Y. FEMS Microbiol. Rev. 2007, 31, 278–292.
Rawat, M.; Newton, G. L.; Ko, M.; Martinez, G. J.; Fahey, R. C.; Av-Gay, Y. Antimicrob. Agents Chemother. 2002, 46, 3348–3355.
Knapp, S.; Gonzalez, S.; Myers, D. S.; Eckman, L. L.; Bewley, C. A. Org. Lett. 2002, 4, 4337–4339.
Metaferia, B. B.; Ray, S.; Smith, J. A.; Bewley, C. A. Bioorg. Med. Chem. Lett. 2007, 17, 444–447.
Newton, G. L.; Leung, S. S.; Wakabayashi, J. I.; Rawat, M.; Fahey, R. C. Biochemistry 2011, 50, 10751–10760.