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 Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by He, H. Articles by Zahrt, T. C. Search for Related Content PubMed PubMed Citation Articles by He, H. Articles by Zahrt, T. C.

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, Jason Kane,² Vineet Singh,^1, and Thomas C. Zahrt^1*

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.

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

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

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

This article has been cited by other articles:

• Hett, E. C., Rubin, E. J. (2008). Bacterial Growth and Cell Division: a Mycobacterial Perspective. Microbiol. Mol. Biol. Rev. 72: 126-156 [Abstract] [Full Text]  
• Lee, J.-H., Karakousis, P. C., Bishai, W. R. (2008). Roles of SigB and SigF in the Mycobacterium tuberculosis Sigma Factor Network. J. Bacteriol. 190: 699-707 [Abstract] [Full Text]  
• Pang, X., Howard, S. T. (2007). Regulation of the {alpha}-Crystallin Gene acr2 by the MprAB Two-Component System of Mycobacterium tuberculosis. J. Bacteriol. 189: 6213-6221 [Abstract] [Full Text]  
• Pang, X., Vu, P., Byrd, T. F., Ghanny, S., Soteropoulos, P., Mukamolova, G. V., Wu, S., Samten, B., Howard, S. T. (2007). Evidence for complex interactions of stress-associated regulons in an mprAB deletion mutant of Mycobacterium tuberculosis. Microbiology 153: 1229-1242 [Abstract] [Full Text]