This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Vandal, O. H.
Right arrow Articles by Ehrt, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Vandal, O. H.
Right arrow Articles by Ehrt, S.

 Previous Article  |  Next Article 

Journal of Bacteriology, January 2009, p. 625-631, Vol. 191, No. 2
0021-9193/09/$08.00+0     doi:10.1128/JB.00932-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Acid-Susceptible Mutants of Mycobacterium tuberculosis Share Hypersusceptibility to Cell Wall and Oxidative Stress and to the Host Environment{triangledown}

Omar H. Vandal, Julia A. Roberts, Toshiko Odaira, Dirk Schnappinger, Carl F. Nathan, and Sabine Ehrt*

Department of Microbiology and Immunology, Weill Cornell Medical College, New York, New York 10065

Received 8 July 2008/ Accepted 5 November 2008

Mycobacterium tuberculosis can persist in macrophage phagosomes that acidify to a pH of ~4.5 after activation of the macrophage with gamma interferon. How the bacterium resists the low pH of the acidified phagosome is incompletely understood. A screen of 10,100 M. tuberculosis transposon mutants for mutants hypersensitive to pH 4.5 led to the discovery of 21 genes whose disruption attenuated survival of M. tuberculosis at a low pH (41). Here, we show that acid-sensitive M. tuberculosis mutants with transposon insertions in Rv2136c, Rv2224c, ponA2, and lysX were hypersensitive to antibiotics, sodium dodecyl sulfate, heat shock, and reactive oxygen and nitrogen intermediates, indicating that acid resistance can be associated with protection against other forms of stress. The Rv2136c mutant was impaired in intrabacterial pH homeostasis and unable to maintain a neutral intrabacterial pH in activated macrophages. The Rv2136c, Rv2224c, and ponA2 mutants were attenuated in mice, with the Rv2136c mutant displaying the most severe level of attenuation. Pathways utilized by M. tuberculosis for acid resistance and intrabacterial pH maintenance are potential targets for chemotherapy.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Weill Cornell Medical College, 1300 York Avenue, A-275A, Box 62, New York, NY 10065. Phone: (212) 746-2994. Fax: (212) 746-8587. E-mail: sae2004{at}med.cornell.edu

{triangledown} Published ahead of print on 14 November 2008.

Journal of Bacteriology, January 2009, p. 625-631, Vol. 191, No. 2
0021-9193/09/$08.00+0     doi:10.1128/JB.00932-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Vandal, O. H., Nathan, C. F., Ehrt, S. (2009). Acid Resistance in Mycobacterium tuberculosis. J. Bacteriol. 191: 4714-4721 [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»