Regulation of the SigH stress response regulon by an essential protein kinase in Mycobacterium tuberculosis.

Proceedings of the National Academy of Sciences of the United States of America
Sang Tae ParkR N Husson

Abstract

SigH is a key regulator of an extensive transcriptional network that responds to oxidative, nitrosative, and heat stresses in Mycobacterium tuberculosis, and this sigma factor is required for virulence in animal models of infection. SigH is negatively regulated by RshA, its cognate anti-sigma factor, which functions as a stress sensor and redox switch. While RshA provides a direct mechanism for sensing stress and activating transcription, bacteria use several types of signal transduction systems to sense the external environment. M. tuberculosis encodes several serine-threonine protein kinase signaling molecules, 2 of which, PknA and PknB, are essential and have been shown to regulate cell morphology and cell wall synthesis. In this work, we demonstrate that SigH and RshA are phosphorylated in vitro and in vivo by PknB. We show that phosphorylation of RshA, but not SigH, interferes with the interaction of these 2 proteins in vitro. Consistent with this finding, negative regulation of SigH activity by RshA in vivo is partially relieved in strains in which pknB is over-expressed, resulting in increased resistance to oxidative stress. These findings demonstrate an interaction between the signaling pathways mediated by PknB and the...Continue Reading

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Citations

May 22, 2009·The Journal of Biological Chemistry·Martin Cohen-GonsaudVirginie Molle
Jul 30, 2009·The Journal of Biological Chemistry·Divya TiwariVinay Kumar Nandicoori
Aug 13, 2010·The Journal of Infectious Diseases·Smriti MehraDeepak Kaushal
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Mar 5, 2011·Microbiology and Molecular Biology Reviews : MMBR·Sandro F F PereiraJonathan Dworkin
Sep 1, 2012·PloS One·Shiva KumarKunchithapadam Swaminathan
Aug 4, 2011·PLoS Pathogens·Stavroula K Hatzios, Carolyn R Bertozzi
Dec 7, 2013·Proceedings of the National Academy of Sciences of the United States of America·Stavroula K HatziosCarolyn R Bertozzi
Aug 28, 2012·Free Radical Biology & Medicine·Shabir Ahmad BhatAshwani Kumar
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Jul 4, 2019·Molecular Microbiology·Joo-Hong ParkJung-Hye Roe

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