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Infection and Immunity, January 2007, p. 452-461, Vol. 75, No. 1
0019-9567/07/$08.00+0     doi:10.1128/IAI.01395-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Characterization of the Mycobacterium tuberculosis Sigma Factor SigM by Assessment of Virulence and Identification of SigM-Dependent Genes{triangledown}

Nisheeth Agarwal, Samuel C. Woolwine, Sandeep Tyagi, and William R. Bishai*

Department of Medicine, Johns Hopkins University, CRB2, Room 1.08, 1550 Orleans Street, Baltimore, Maryland 21231-1044

Received 30 August 2006/ Returned for modification 12 October 2006/ Accepted 26 October 2006

Alternate sigma factors have been implicated in the survival of mycobacteria in response to specific stresses. To characterize the role of SigM in Mycobacterium tuberculosis, a sigM deletion mutant was generated by allelic exchange in the virulent CDC1551 strain. Comparing the wild-type and {Delta}sigM strains by complete genomic microarray, we observed a low level of baseline expression of sigM in wild-type M. tuberculosis and no significant differences in the gene expression patterns between these two strains. Alternatively, a SigM-overexpressing M. tuberculosis strain was constructed and microarray profiling revealed SigM-dependent expression of a relatively small group of genes, which included four esat-6 homologues: esxE, esxF, esxT, and esxU. An assessment of SigM-dependent promoters from the microarray analysis revealed a putative consensus sequence for M. tuberculosis SigM of –35 GGAAC and –10 CGTCR. In vitro expression studies showed that M. tuberculosis sigM transcripts accumulate slightly in stationary phase and following heat shock. To understand the role of SigM in pathogenesis, the M. tuberculosis sigM deletion strain was compared with the isogenic wild-type strain and the complemented mutant strain for survival in murine macrophages and in the mouse model. The mutant was found to have similar abilities to survive in both the resting and activated J774A.1 macrophages. Mouse organ bacterial burdens indicated that the mutant proliferated and persisted at the same level as that of the wild-type and complemented strains in lung and spleen tissues. In time-to-death experiments in the mouse model, the {Delta}sigM mutant exhibited lethality times comparable to those observed for the wild-type and complemented strains. These data indicate that M. tuberculosis SigM governs the expression of a small set of genes, including four esat-6 homologues, and that the loss of sigM does not confer a detectable virulence defect in the macrophages and mouse models of infection.

* Corresponding author. Mailing address: Dept. of Medicine, Division of Infectious Diseases, Johns Hopkins School of Medicine, CRB2 Room 1.08, 1550 Orleans Street, Baltimore, Maryland 21231-1044. Phone: (410) 955-3507. Fax: (410) 614-8173. E-mail: wbishai{at}jhmi.edu.

{triangledown} Published ahead of print on 6 November 2006.

Editor: W. A. Petri, Jr.

Infection and Immunity, January 2007, p. 452-461, Vol. 75, No. 1
0019-9567/07/$08.00+0     doi:10.1128/IAI.01395-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • 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]  
  • Nakunst, D., Larisch, C., Huser, A. T., Tauch, A., Puhler, A., Kalinowski, J. (2007). The Extracytoplasmic Function-Type Sigma Factor SigM of Corynebacterium glutamicum ATCC 13032 Is Involved in Transcription of Disulfide Stress-Related Genes. J. Bacteriol. 189: 4696-4707 [Abstract] [Full Text]  
  • Williams, E. P., Lee, J.-H., Bishai, W. R., Colantuoni, C., Karakousis, P. C. (2007). Mycobacterium tuberculosis SigF Regulates Genes Encoding Cell Wall-Associated Proteins and Directly Regulates the Transcriptional Regulatory Gene phoY1. J. Bacteriol. 189: 4234-4242 [Abstract] [Full Text]  


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