title: Mycobacterium leprae is naturally resistant to PA-824.
abstract: 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.
authors.affiliation: Tuberculosis Research Section, National Institute of Allergy and Infectious Diseases, Rockville, MD 20852, USA.
authors.forename: Ujjini H
authors.initials: UH
authors.lastname: Manjunatha
authors.forename: Ramanuj
authors.initials: R
authors.lastname: Lahiri
authors.forename: Baljit
authors.initials: B
authors.lastname: Randhawa
authors.forename: Cynthia S
authors.initials: CS
authors.lastname: Dowd
authors.forename: James L
authors.initials: JL
authors.lastname: Krahenbuhl
authors.forename: Clifton E
authors.initials: CE
authors.lastname: Barry
mesh_terms: D000818:Animals; D003470:Culture Media; D004195:Disease Models, Animal; D024881:Drug Resistance, Bacterial; D007918:Leprosy / Q000188:drug therapy / Q000382:microbiology; D017737:Macrophages, Peritoneal / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008826:Microbial Sensitivity Tests; D009166:Mycobacterium leprae / Q000187:drug effects* / Q000254:growth & development; D009593:Nitroimidazoles / Q000494:pharmacology*
chemical_list: D003470:Culture Media; D009593:Nitroimidazoles; C410767:pretomanid