This Article Full Text Full Text (PDF) Supplemental material Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Converse, P. J. Articles by Bishai, W. R. Search for Related Content PubMed PubMed Citation Articles by Converse, P. J. Articles by Bishai, W. R.

 Previous Article  |  Next Article 

Infection and Immunity, March 2009, p. 1230-1237, Vol. 77, No. 3
0019-9567/09/$08.00+0     doi:10.1128/IAI.01117-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Role of the dosR-dosS Two-Component Regulatory System in Mycobacterium tuberculosis Virulence in Three Animal Models ^,

Paul J. Converse,^1* Petros C. Karakousis,¹ Lee G. Klinkenberg,¹ Anup K. Kesavan,¹ Lan H. Ly,² Shannon Sedberry Allen,^2, Jacques H. Grosset,¹ Sanjay K. Jain,¹ Gyanu Lamichhane,¹ Yukari C. Manabe,¹ David N. McMurray,² Eric L. Nuermberger,¹ and William R. Bishai¹

Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, Maryland,¹ Department of Microbial and Molecular Pathogenesis, Texas A&M University System Health Science Center, College Station, Texas 77843²

Received 6 September 2008/ Returned for modification 11 October 2008/ Accepted 14 December 2008

The Mycobacterium tuberculosis dosR gene (Rv3133c) is part of an operon, Rv3134c-Rv3132c, and encodes a response regulator that has been shown to be upregulated by hypoxia and other in vitro stress conditions and may be important for bacterial survival within granulomatous lesions found in tuberculosis. DosR is activated in response to hypoxia and nitric oxide by DosS (Rv3132c) or DosT (Rv2027c). We compared the virulence levels of an M. tuberculosis dosR-dosS deletion mutant (dosR-dosS [dosR-S]), a dosR-complemented strain, and wild-type H37Rv in rabbits, guinea pigs, and mice infected by the aerosol route and in a mouse hollow-fiber model that may mimic in vivo granulomatous conditions. In the mouse and the guinea pig models, the dosR-S mutant exhibited a growth defect. In the rabbit, the dosR-S mutant did not replicate more than the wild type. In the hollow-fiber model, the mutant phenotype was not different from that of the wild-type strain. Our analyses reveal that the dosR and dosS genes are required for full virulence and that there may be differences in the patterns of attenuation of this mutant between the animal models studied.

---

* Corresponding author. Mailing address: Center for Tuberculosis Research, 1550 Orleans Street, Room 103, Baltimore, MD 21231. Phone: (410) 502-8236. Fax: (410) 614-8173. E-mail: pconvers{at}jhsph.edu

Published ahead of print on 22 December 2008.

Supplemental material for this article may be found at http://iai.asm.org/.

Editor: W. A. Petri, Jr.

Present address: Department of Medicine, Division of Infectious Diseases, Vanderbilt University School of Medicine, Nashville, TN.

---

Infection and Immunity, March 2009, p. 1230-1237, Vol. 77, No. 3
0019-9567/09/$08.00+0     doi:10.1128/IAI.01117-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

This article has been cited by other articles:

• Fontan, P. A., Voskuil, M. I., Gomez, M., Tan, D., Pardini, M., Manganelli, R., Fattorini, L., Schoolnik, G. K., Smith, I. (2009). The Mycobacterium tuberculosis Sigma Factor {sigma}B Is Required for Full Response to Cell Envelope Stress and Hypoxia In Vitro, but It Is Dispensable for In Vivo Growth. J. Bacteriol. 191: 5628-5633 [Abstract] [Full Text]