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Infection and Immunity, January 1999, p. 460-465, Vol. 67, No. 1
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Response to Reactive Nitrogen Intermediates in Mycobacterium tuberculosis: Induction of the 16-Kilodalton alpha -Crystallin Homolog by Exposure to Nitric Oxide Donors

T. R. Garbe,1 N. S. Hibler,1 and V. Deretic2,*

Department of Microbiology and Immunology, University of Texas Health Science Center San Antonio, San Antonio, Texas 78284,1 and Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan 48109-06202

Received 1 June 1998/Returned for modification 17 July 1998/Accepted 23 October 1998

In contrast to the apparent paucity of Mycobacterium tuberculosis response to reactive oxygen intermediates, this organism has evolved a specific response to nitric oxide challenge. Exposure of M. tuberculosis to NO donors induces the synthesis of a set of polypeptides that have been collectively termed Nox. In this work, the most prominent Nox polypeptide, Nox16, was identified by immunoblotting and by N-terminal sequencing as the alpha -crystallin-related, 16-kDa small heat shock protein, sHsp16. A panel of chemically diverse donors of nitric oxide, with the exception of nitroprusside, induced sHsp16 (Nox16). Nitroprusside, a coordination complex of Fe2+ with a nitrosonium (NO+) ion, induced a 19-kDa polypeptide (Nox19) homologous to the nonheme bacterial ferritins. We conclude that the NO response in M. tuberculosis is dominated by increased synthesis of the alpha -crystallin homolog sHsp16, previously implicated in stationary-phase processes and found in this study to be a major M. tuberculosis protein induced upon exposure to reactive nitrogen intermediates.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, 5641 Medical Science Building II, University of Michigan Medical School, Ann Arbor, MI 48109-0620. Phone: (734) 763-1580. Fax: (734) 647-6243. E-mail: Deretic{at}umich.edu.

Infection and Immunity, January 1999, p. 460-465, Vol. 67, No. 1
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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