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Journal of Bacteriology, October 2009, p. 5941-5952, Vol. 191, No. 19
0021-9193/09/$08.00+0     doi:10.1128/JB.00778-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

mosR, a Novel Transcriptional Regulator of Hypoxia and Virulence in Mycobacterium tuberculosis{triangledown} ,{dagger}

Bassam Abomoelak,1 Elizabeth A. Hoye,1 Jing Chi,1 Sarah A. Marcus,1 Francoise Laval,2,3 John P. Bannantine,4 Sarah K. Ward,1 Mamadou Daffé,2,3 Hong Di Liu,1 and Adel M. Talaat1,5*

Laboratory of Bacterial Genomics, Department of Pathobiological Sciences, University of Wisconsin—Madison, 1656 Linden Drive, Madison, Wisconsin 53706,1 CNRS, Institut de Pharmacologie et de Biologie Structurale,2 Paul Sabatier University, 205 Route de Narbonne, 31077 Toulouse Cedex, France,3 National Animal Disease Center, Ames, Iowa,4 Department of Food Hygiene, Faculty of Veterinary Medicine, Cairo University, Cairo, Egypt5

Received 15 June 2009/ Accepted 20 July 2009

Latent tuberculosis represents a high-risk burden for one-third of the world population. Previous analysis of murine tuberculosis identified a novel transcriptional regulator encoded by Rv0348 that could control the establishment of persistent tuberculosis. Disruption of the Rv0348 gene from the genome of the virulent H37Rv strain of Mycobacterium tuberculosis revealed a global impact on the transcriptional profiles of 163 genes, including induction of the mammalian cell entry (mce1) operon and the repression of a significant number of genes involved in hypoxia and starvation responses. Nonetheless, gel shift assays did not reveal direct binding between Rv0348 and a set of regulated promoters, suggesting an indirect regulatory role. However, when expressed in Mycobacterium smegmatis, the Rv0348 transcripts were significantly responsive to different levels of hypoxia and the encoded protein was shown to regulate genes involved in hypoxia [e.g., Rv3130c (tgs1)] and intracellular survival (e.g., mce1), among other genes. Interestingly, the colonization level of the {Delta}mosR mutant strain was significantly lower than that of the wild-type strain of M. tuberculosis, suggesting its attenuation in the murine model of tuberculosis. Taken together, our analyses indicated that the Rv0348 gene encodes a novel transcriptional factor that regulates several operons involved in mycobacterial survival, especially during hypoxia; hence, we propose that Rv0348 be renamed mosR for regulator of mycobacterial operons of survival.

* Corresponding author. Mailing address: The Laboratory of Bacterial Genomics, Department of Pathobiological Sciences, University of Wisconsin—Madison, Room 303, 1656 Linden Drive, Madison, WI 53706. Phone: (608) 262-2861. Fax: (608) 262-7420. E-mail: atalaat{at}wisc.edu

{triangledown} Published ahead of print on 31 July 2009.

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

Journal of Bacteriology, October 2009, p. 5941-5952, Vol. 191, No. 19
0021-9193/09/$08.00+0     doi:10.1128/JB.00778-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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