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Journal of Bacteriology, March 2006, p. 2134-2143, Vol. 188, No. 6
0021-9193/06/$08.00+0     doi:10.1128/JB.188.6.2134-2143.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

MprAB Is a Stress-Responsive Two-Component System That Directly Regulates Expression of Sigma Factors SigB and SigE in Mycobacterium tuberculosis§

Hongjun He,1 Raymond Hovey,1,{dagger} Jason Kane,2 Vineet Singh,1,{ddagger} and Thomas C. Zahrt1*

Department of Microbiology and Molecular Genetics,1 Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin 532262

Received 22 August 2005/ Accepted 18 December 2005

The genetic mechanisms mediating the adaptation of Mycobacterium tuberculosis within the host are poorly understood. The best-characterized regulatory systems in this organism include sigma factors and two-component signal transduction systems. mprAB is a two-component system required by M. tuberculosis for growth in vivo during the persistent stage of infection. In this report, we demonstrate that MprAB is stress responsive and regulates the expression of numerous stress-responsive genes in M. tuberculosis. With DNA microarrays and quantitative real-time reverse transcription-PCR, genes regulated by MprA in M. tuberculosis that included two stress-responsive sigma factors were identified. Response regulator MprA bound to conserved motifs in the upstream regions of both sigB and sigE in vitro and regulated the in vivo expression of sigB and sigE in M. tuberculosis. In addition, mprA itself was induced following exposure to stress, establishing a direct role for this regulatory system in stress response pathways of M. tuberculosis. Induction of mprA and sigE by MprA in response to stress was mediated through the cognate sensor kinase MprB and required expression of the extracytoplasmic loop domain. These results provide the first evidence that recognition of and adaptation to specific stress in M. tuberculosis are mediated through activation of a two-component signal transduction system that directly regulates the expression of stress-responsive determinants.

* Corresponding author. Mailing address: Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, WI 53226. Phone: (414) 456-7429. Fax: (414) 456-6535. E-mail: tzahrt{at}mcw.edu.

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

{dagger} Present address: Department of Biological Sciences, University of Wisconsin at Milwaukee, Milwaukee, WI 53201.

{ddagger} Present address: Department of Microbiology and Immunology, Kirksville School of Osteopathic Medicine, Kirksville, MO 63501.

Journal of Bacteriology, March 2006, p. 2134-2143, Vol. 188, No. 6
0021-9193/06/$08.00+0     doi:10.1128/JB.188.6.2134-2143.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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