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Antimicrobial Agents and Chemotherapy, October 2006, p. 3350-3354, Vol. 50, No. 10
0066-4804/06/$08.00+0     doi:10.1128/AAC.00488-06

Mycobacterium leprae Is Naturally Resistant to PA-824

Ujjini H. Manjunatha,1 Ramanuj Lahiri,2 Baljit Randhawa,2 Cynthia S. Dowd,1 James L. Krahenbuhl,2 and Clifton E. Barry III1*

Tuberculosis Research Section, National Institute of Allergy and Infectious Diseases, 12441 Parklawn Drive, Twinbrook II, Rockville, Maryland,1 Laboratory Research Branch, National Hansen's Disease Programs, Louisiana State University, Skip Bertman Drive, Baton Rouge, Louisiana 708032

Received 19 April 2006/ Returned for modification 5 June 2006/ Accepted 13 July 2006

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.

* Corresponding author. Mailing address: Tuberculosis Research Section, National Institute of Allergy and Infectious Diseases, 12441 Parklawn Drive, Twinbrook II, Rockville, MD 20852. Phone: (301) 435-7509. Fax: (301) 402-0993. E-mail: cbarry{at}niaid.nih.gov.

Antimicrobial Agents and Chemotherapy, October 2006, p. 3350-3354, Vol. 50, No. 10
0066-4804/06/$08.00+0     doi:10.1128/AAC.00488-06




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