Leprosy responds very slowly to the current multidrug therapy, and hence there is a need for novel drugs with potent bactericidal activity. PA-824 is a 4-nitroimidazo-oxazine that is currently undergoing phase I clinical trials for the treatment of tuberculosis. The activity of PA-824 against Mycobacterium leprae was tested and compared with that of rifampin in axenic cultures, macrophages, and two different animal models. Our results conclusively demonstrate that PA-824 has no effect on the viability of M. leprae in all three models, consistent with the lack of the nitroimidazo-oxazine-specific nitroreductase, encoded by Rv3547 in the M. leprae genome, which is essential for activation of this molecule.
BT - Antimicrobial agents and chemotherapy C1 - http://www.ncbi.nlm.nih.gov/pubmed/17005816?dopt=Abstract DA - 2006 Oct DO - 10.1128/AAC.00488-06 IS - 10 J2 - Antimicrob. Agents Chemother. LA - eng N2 -Leprosy responds very slowly to the current multidrug therapy, and hence there is a need for novel drugs with potent bactericidal activity. PA-824 is a 4-nitroimidazo-oxazine that is currently undergoing phase I clinical trials for the treatment of tuberculosis. The activity of PA-824 against Mycobacterium leprae was tested and compared with that of rifampin in axenic cultures, macrophages, and two different animal models. Our results conclusively demonstrate that PA-824 has no effect on the viability of M. leprae in all three models, consistent with the lack of the nitroimidazo-oxazine-specific nitroreductase, encoded by Rv3547 in the M. leprae genome, which is essential for activation of this molecule.
PY - 2006 SP - 3350 EP - 4 T2 - Antimicrobial agents and chemotherapy TI - Mycobacterium leprae is naturally resistant to PA-824. UR - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1610092/pdf/0488-06.pdf VL - 50 SN - 0066-4804 ER -