This Article Full Text Full Text (PDF) 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 Zahrt, T. C. Articles by Trevett, A. Search for Related Content PubMed PubMed Citation Articles by Zahrt, T. C. Articles by Trevett, A.

Functional Analysis of the Mycobacterium tuberculosis MprAB Two-Component Signal Transduction System

Thomas C. Zahrt,^* Christopher Wozniak, Denise Jones, and Andrea Trevett

Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin 53226

Received 8 May 2003/ Returned for modification 22 July 2003/ Accepted 2 September 2003

The mechanisms utilized by Mycobacterium tuberculosis to establish, maintain, or reactivate from latent infection in the host are largely unknown but likely include genes that mediate adaptation to conditions encountered during persistence. Previously, a two-component signal transduction system, mprAB, was found to be required in M. tuberculosis for establishment and maintenance of persistent infection in a tissue- and stage-specific fashion. To begin to characterize the role of this system in M. tuberculosis physiology and virulence, a functional analysis of the mprA and mprB gene products was initiated. Here, evidence is presented demonstrating that sensor kinase MprB and response regulator MprA function as an intact signal-transducing pair in vitro and in vivo. Sensor kinase MprB can be autophosphorylated, can donate phosphate to MprA, and can act as a phospho-MprA phosphatase in vitro. Correspondingly, response regulator MprA can accept phosphate from MprB or from small phosphodonors including acetyl phosphate. Mutagenesis of residues His249 in MprB and Asp48 in MprA abolished the ability of these proteins to be phosphorylated in vitro. Introduction of these alleles into Mycobacterium bovis BCGattenuated virulence in macrophages in vivo. Together, these results support a role for the mprAB two-component system in M. tuberculosis physiology and pathogenesis. Characterization of two-component signal transduction systems will enhance our understanding of processes regulated by M. tuberculosis during acute and/or persistent infection in the host.

Editor: V. J. DiRita

Present address: Department of Microbiology, University of Washington, Seattle, Wash.

Present address: Department of Bacteriology, University of Wisconsin, Madison, Wis.

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]  
• 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]  
• Glover, R. T., Kriakov, J., Garforth, S. J., Baughn, A. D., Jacobs, W. R. Jr. (2007). The Two-Component Regulatory System senX3-regX3 Regulates Phosphate-Dependent Gene Expression in Mycobacterium smegmatis. J. Bacteriol. 189: 5495-5503 [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]  
• He, H., Hovey, R., Kane, J., Singh, V., Zahrt, T. C. (2006). MprAB Is a Stress-Responsive Two-Component System That Directly Regulates Expression of Sigma Factors SigB and SigE in Mycobacterium tuberculosis. J. Bacteriol. 188: 2134-2143 [Abstract] [Full Text]  
• Gazdik, M. A., McDonough, K. A. (2005). Identification of Cyclic AMP-Regulated Genes in Mycobacterium tuberculosis Complex Bacteria under Low-Oxygen Conditions. J. Bacteriol. 187: 2681-2692 [Abstract] [Full Text]  
• Wolfe, A. J. (2005). The Acetate Switch. Microbiol. Mol. Biol. Rev. 69: 12-50 [Abstract] [Full Text]  
• He, H., Zahrt, T. C. (2005). Identification and Characterization of a Regulatory Sequence Recognized by Mycobacterium tuberculosis Persistence Regulator MprA. J. Bacteriol. 187: 202-212 [Abstract] [Full Text]  
• Saini, D. K., Malhotra, V., Dey, D., Pant, N., Das, T. K., Tyagi, J. S. (2004). DevR-DevS is a bona fide two-component system of Mycobacterium tuberculosis that is hypoxia-responsive in the absence of the DNA-binding domain of DevR. Microbiology 150: 865-875 [Abstract] [Full Text]