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Journal of Clinical Microbiology, September 2002, p. 3162-3166, Vol. 40, No. 9
0095-1137/02/$04.00+0     DOI: 10.1128/JCM.40.9.3162-3166.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Reactive Nitrogen Intermediates Have a Bacteriostatic Effect on Mycobacterium tuberculosis In Vitro

Marcia A. Firmani and Lee W. Riley*

School of Public Health, Division of Infectious Diseases, University of California at Berkeley, Berkeley, California 94720

Received 6 February 2002/ Returned for modification 18 May 2002/ Accepted 22 June 2002

Susceptibility of six isolates of Mycobacterium tuberculosis (CB3.3, CDC1551, RJ2E, C.C.13, H37Rv, and H37Ra) and two isolates of Mycobacterium bovis (Ravenel and BCG) to reactive oxygen intermediates (ROI) and reactive nitrogen intermediates (RNI) was determined by standard in vitro survival assays. After 21 days of incubation, the survival of most strains exposed to either acidified sodium nitrite (ASN) or hydrogen peroxide (H2O2) was significantly lower than the same strains unexposed to these RNI or ROI products. However, after 50 days of incubation, these differences in susceptibility became less apparent for strains exposed to ASN but not for strains exposed to H2O2. The recovery of these strains after exposure to RNI suggests that the effect of RNI on M. tuberculosis is bacteriostatic. The in vitro concentrations of ROI and RNI used in these assays were higher than those expected in vivo. These observations suggest that, in vivo, RNI expression at physiologically achievable concentrations may keep M. tuberculosis from proliferating but that removal of RNI may allow the organisms to proliferate. Furthermore, the ability of some M. tuberculosis strains to cause rapidly progressive disease may relate to their intrinsic levels of RNI and ROI resistance.


* Corresponding author. Mailing address: School of Public Health, Division of Infectious Diseases, 140 Warren Hall, University of California, Berkeley, Berkeley, CA 94720. Phone: (510) 642-9200. Fax: (510) 642-6350. E-mail: lwriley{at}uclink4.berkeley.edu.


Journal of Clinical Microbiology, September 2002, p. 3162-3166, Vol. 40, No. 9
0095-1137/02/$04.00+0     DOI: 10.1128/JCM.40.9.3162-3166.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.




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