01634nas a2200349   4500000000100000008004100001260001300042653001200055653001800067653002700085653003100112653001200143653002800155653000900183653002400192653001500216653003200231653002500263653002000288100001800308700001300326700001500339700001100354700001800365700001200383245005900395856007300454300001100527490000700538520072500545022001401270       2006                            d  c2006 Oct10aAnimals10aCulture Media10aDisease Models, Animal10aDrug Resistance, Bacterial10aleprosy10aMacrophages, Peritoneal10aMice10aMice, Inbred BALB C10aMice, Nude10aMicrobial Sensitivity Tests10aMycobacterium leprae10aNitroimidazoles1 aManjunatha UH1 aLahiri R1 aRandhawa B1 aDowd C1 aKrahenbuhl JL1 aBarry C00aMycobacterium leprae is naturally resistant to PA-824.  uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1610092/pdf/0488-06.pdf  a3350-40 v503 a<p>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.</p>  a0066-4804