This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sharma, K.
Right arrow Articles by Singh, Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sharma, K.
Right arrow Articles by Singh, Y.

 Previous Article  |  Next Article 

Journal of Bacteriology, April 2006, p. 2936-2944, Vol. 188, No. 8
0021-9193/06/$08.00+0     doi:10.1128/JB.188.8.2936-2944.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Transcriptional Control of the Mycobacterial embCAB Operon by PknH through a Regulatory Protein, EmbR, In Vivo

Kirti Sharma, Meetu Gupta, Monika Pathak, Nidhi Gupta, Anil Koul,{dagger} Smilona Sarangi, Renu Baweja, and Yogendra Singh*

Institute of Genomics and Integrative Biology, Mall Road, Delhi, India

Received 6 December 2005/ Accepted 2 February 2006

EmbR, a putative transcriptional regulator from Mycobacterium tuberculosis, is homologous to the OmpR class of transcriptional regulators that possess winged helix-turn-helix DNA binding motifs. In contrast to other OmpR-like response regulators that are usually phosphorylated and controlled by histidine kinases, EmbR was recently shown to be phosphorylated by the cognate mycobacterial serine/threonine kinase PknH. Despite the in vitro evidence of phosphorylation and interaction between the kinase and regulator, the physiological function of the PknH-EmbR pair is still unknown. We identify the embCAB operon encoding arabinosyltransferases in M. tuberculosis as the cellular target of EmbR. Phosphorylation of EmbR enhances its DNA binding activity towards promoter regions of embCAB genes. In vivo studies involving expression of PknH in Mycobacterium smegmatis established its positive regulatory effect on transcription of the embCAB operon via phosphorylation of EmbR. Interestingly, increased transcription of embC, catalyzing arabinosylation of lipomannan (LM) to lipoarabinomannan (LAM), results in a high LAM/LM ratio, which in turn is a crucial factor in mycobacterial virulence. The PknH-mediated increase in the transcription of embAB genes significantly alters resistance to ethambutol, a frontline antituberculosis drug known to target embAB genes. These findings and in vivo upregulation of PknH inside the host macrophages suggest a functionally relevant signaling mechanism involving the PknH-EmbR-embCAB system.

* Corresponding author. Mailing address: IGIB, Mall Road, Delhi 110 007, India. Phone: 91 11 2766 6156. Fax: 91 11 2766 7471. E-mail: ysingh{at}igib.res.in.

{dagger} Present address: Department of Antimicrobial Research, Johnson & Johnson Pharmaceutical Research and Development, Beerse, Belgium.

Journal of Bacteriology, April 2006, p. 2936-2944, Vol. 188, No. 8
0021-9193/06/$08.00+0     doi:10.1128/JB.188.8.2936-2944.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Tiwari, D., Singh, R. K., Goswami, K., Verma, S. K., Prakash, B., Nandicoori, V. K. (2009). Key Residues in Mycobacterium tuberculosis Protein Kinase G Play a Role in Regulating Kinase Activity and Survival in the Host. J. Biol. Chem. 284: 27467-27479 [Abstract] [Full Text]  
  • Cohen-Gonsaud, M., Barthe, P., Canova, M. J., Stagier-Simon, C., Kremer, L., Roumestand, C., Molle, V. (2009). The Mycobacterium tuberculosis Ser/Thr Kinase Substrate Rv2175c Is a DNA-binding Protein Regulated by Phosphorylation. J. Biol. Chem. 284: 19290-19300 [Abstract] [Full Text]  
  • Kumar, P., Kumar, D., Parikh, A., Rananaware, D., Gupta, M., Singh, Y., Nandicoori, V. K. (2009). The Mycobacterium tuberculosis Protein Kinase K Modulates Activation of Transcription from the Promoter of Mycobacterial Monooxygenase Operon through Phosphorylation of the Transcriptional Regulator VirS. J. Biol. Chem. 284: 11090-11099 [Abstract] [Full Text]  
  • Veyron-Churlet, R., Molle, V., Taylor, R. C., Brown, A. K., Besra, G. S., Zanella-Cleon, I., Futterer, K., Kremer, L. (2009). The Mycobacterium tuberculosis {beta}-Ketoacyl-Acyl Carrier Protein Synthase III Activity Is Inhibited by Phosphorylation on a Single Threonine Residue. J. Biol. Chem. 284: 6414-6424 [Abstract] [Full Text]  
  • Goude, R., Amin, A. G., Chatterjee, D., Parish, T. (2008). The Critical Role of embC in Mycobacterium tuberculosis. J. Bacteriol. 190: 4335-4341 [Abstract] [Full Text]  
  • Amin, A. G., Goude, R., Shi, L., Zhang, J., Chatterjee, D., Parish, T. (2008). EmbA is an essential arabinosyltransferase in Mycobacterium tuberculosis. Microbiology 154: 240-248 [Abstract] [Full Text]  
  • Chauhan, N., Kruppa, M., Calderone, R. (2007). The Ssk1p Response Regulator and Chk1p Histidine Kinase Mutants of Candida albicans Are Hypersensitive to Fluconazole and Voriconazole. Antimicrob. Agents Chemother. 51: 3747-3751 [Abstract] [Full Text]  
  • Roback, P., Beard, J., Baumann, D., Gille, C., Henry, K., Krohn, S., Wiste, H., Voskuil, M.I., Rainville, C., Rutherford, R. (2007). A predicted operon map for Mycobacterium tuberculosis. Nucleic Acids Res 35: 5085-5095 [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]  
  • Narayan, A., Sachdeva, P., Sharma, K., Saini, A. K., Tyagi, A. K., Singh, Y. (2007). Serine threonine protein kinases of mycobacterial genus: phylogeny to function. Physiol. Genomics 29: 66-75 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»