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Journal of Bacteriology, June 2009, p. 3965-3980, Vol. 191, No. 12
0021-9193/09/$08.00+0     doi:10.1128/JB.00064-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Functional Genomics Reveals Extended Roles of the Mycobacterium tuberculosis Stress Response Factor ^H

Smriti Mehra^1, and Deepak Kaushal^1,2,3,*

Division of Bacteriology and Parasitology, DNA Microarray and Expression Core, Tulane National Primate Research Center, Covington, Louisiana,¹ Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, Louisiana,² Joint Tulane-LSU Center for Experimental Infectious Disease Research, Louisiana State University School of Veterinary Medicine, Baton Rouge, Louisiana³

Received 17 January 2009/ Accepted 7 April 2009

Mycobacterium tuberculosis is one of the most successful pathogens of humankind. During infection, M. tuberculosis must cope with and survive against a variety of different environmental conditions. Sigma factors likely facilitate the modulation of the pathogen's gene expression in response to changes in its extracellular milieu during infection. ^H, an alternate sigma factor encoded by the M. tuberculosis genome, is induced by thiol-oxidative stress, heat shock, and phagocytosis. In response to these conditions, ^H induces the expression of ^B, ^E, and the thioredoxin regulon. In order to more effectively characterize the transcriptome controlled by ^H, we studied the long-term effects of the induction of ^H on global transcription in M. tuberculosis. The M. tuberculosis isogenic mutant of ^H (-^H) is more susceptible to diamide stress than wild-type M. tuberculosis. To study the long-term effects of ^H induction, we exposed both strains to diamide, rapidly washed it away, and resumed culturing in diamide-free medium (post-diamide stress culturing). Analysis of the effects of ^H induction in this experiment revealed a massive temporal programming of the M. tuberculosis transcriptome. Immediately after the induction of ^H, genes belonging to the functional categories "virulence/detoxification" and "regulatory proteins" were induced in large numbers. Fewer genes belonging to the "lipid metabolism" category were induced, while a larger number of genes belonging to this category were downregulated. ^H caused the induction of the ATP-dependent clp proteolysis regulon, likely mediated by a transcription factor encoded by Rv2745c, several members of the mce1 virulence regulon, and the sulfate acquisition/transport network.

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* Corresponding author. Mailing address: Division of Bacteriology and Parasitology, Tulane National Primate Research Center, 18703 Three Rivers Road, Covington, LA 70433. Phone: (985) 871-6254. Fax: (985) 871-6390. E-mail: dkaushal{at}tulane.edu

Published ahead of print on 17 April 2009.

Both authors contributed equally to this work.

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Journal of Bacteriology, June 2009, p. 3965-3980, Vol. 191, No. 12
0021-9193/09/$08.00+0     doi:10.1128/JB.00064-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.