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Infection and Immunity, July 1999, p. 3276-3283, Vol. 67, No. 7
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

noxR3, a Novel Gene from Mycobacterium tuberculosis, Protects Salmonella typhimurium from Nitrosative and Oxidative Stress

Jia Ruan,1 Gregory St. John,1 Sabine Ehrt,2 Lee Riley,2 and Carl Nathan1,*

Department of Microbiology and Immunology and Department of Medicine, Weill Medical College of Cornell University, New York, New York,1 and Division of Public Health Biology & Epidemiology, School of Public Health, University of California, Berkeley, California2

Received 7 December 1998/Returned for modification 28 January 1999/Accepted 12 April 1999

Reactive oxygen intermediates (ROI) and reactive nitrogen intermediates (RNI) produced by activated macrophages participate in host defense against the facultative intracellular pathogens Mycobacterium tuberculosis and Salmonella typhimurium. To survive within macrophages, such pathogens may have evolved ROI and RNI resistance mechanisms. ROI resistance pathways have been intensively studied. Much less is known about the mechanisms of resistance to RNI. To identify possible RNI resistance genes in M. tuberculosis, a mycobacterial library was expressed in S. typhimurium and subjected to selection by exposure to the NO donor S-nitrosoglutathione (GSNO) in concentrations sufficient to kill the vast majority of nontransformed salmonellae. Among the rare surviving recombinants was a clone expressing noxR3, a novel and previously anonymous M. tuberculosis gene predicted to encode a small, basic protein. Expression of noxR3 protected S. typhimurium not only from GSNO and acidified nitrite but also from H2O2. noxR3 is the third gene cloned from M. tuberculosis that has been shown to protect heterologous cells from both RNI and ROI. This suggests diversity in the repertoire of mechanisms that help pathogens resist the oxidative and nitrosative defenses of the host.

* Corresponding author. Mailing address: Box 57, WMCCU, 1300 York Ave., New York, NY 10021. Phone: (212) 746-2985. Fax: (212) 746-8536. E-mail: cnathan{at}mail.med.cornell.edu.

Infection and Immunity, July 1999, p. 3276-3283, Vol. 67, No. 7
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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