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Infection and Immunity, August 2005, p. 4581-4587, Vol. 73, No. 8
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.8.4581-4587.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Role for Nucleotide Excision Repair in Virulence of Mycobacterium tuberculosis

K. Heran Darwin1,{dagger} and Carl F. Nathan1,2*

Department of Microbiology and Immunology, Weill Medical College of Cornell University, 1300 York Avenue, Box 57, New York, New York 10021,1 Graduate Program in Immunology and Microbial Pathogenesis and Graduate Program in Molecular Biology, Weill Graduate School of Medical Sciences of Cornell University, New York, New York2

Received 4 October 2004/ Returned for modification 13 December 2004/ Accepted 18 March 2005

Mutations in Mycobacterium tuberculosis uvrB result in severe sensitivity to acidified nitrite, a source of nitric oxide (6). In this study, we show that a uvrB mutant is exquisitely sensitive to UV light but not to several sources of reactive oxygen species in vitro. Furthermore, a uvrB mutant was attenuated in mice as judged by an extension of life span. Attenuation in mice was partially reversed by genetic inactivation of nitric oxide synthase 2 (iNOS) and almost completely reversed in mice lacking both iNOS and phagocyte oxidase. Thus, a gene predicted to encode a key element of DNA repair is required for resistance of M. tuberculosis to both reactive nitrogen and reactive oxygen species in mice.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Weill Medical College of Cornell University, 1300 York Avenue, Box 57, New York, NY 10021. Phone: (212) 746-6505. Fax: (212) 746-8587. E-mail: cnathan{at}med.cornell.edu.

Editor: V. J. DiRita

{dagger} Present address: Department of Microbiology, New York University School of Medicine, 550 First Avenue, MSB 236, New York, NY 10016.

Infection and Immunity, August 2005, p. 4581-4587, Vol. 73, No. 8
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.8.4581-4587.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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