The two-component signalling networks of Mycobacterium tuberculosis display extensive cross-talk in vitro

Agrawal, Ruchi and Pandey, Akancha and Rajankar, Mayooreshwar P and Dixit, Narendra M and Saini, Deepak K (2015) The two-component signalling networks of Mycobacterium tuberculosis display extensive cross-talk in vitro. In: BIOCHEMICAL JOURNAL, 469 (1). pp. 121-134.

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Abstract

Two-component systems (TCSs), which contain paired sensor kinase and response regulator proteins, form the primary apparatus for sensing and responding to environmental cues in bacteria. TCSs are thought to be highly specific, displaying minimal cross-talk, primarily due to the co-evolution of the participating proteins. To assess the level of cross-talk between the TCSs of Mycobacterium tuberculosis, we mapped the complete interactome of the M. tuberculosis TCSs using phosphotransfer profiling. Surprisingly, we found extensive crosstalk among the M. tuberculosis TCSs, significantly more than that in the TCSs in Escherichia coli or Caulobacter crescentus, thereby offering an alternate to specificity paradigm in TCS signalling. Nearly half of the interactions we detected were significant novel cross-interactions, unravelling a potentially complex signalling landscape. We classified the TCSs into specific `one-to-one' and promiscuous `one-to-many' and `many-to-one' circuits. Using mathematical modelling, we deduced that the promiscuous signalling observed can explain several currently confounding observations about M. tuberculosis TCSs. Our findings suggest an alternative paradigm of bacterial signalling with significant cross-talk between TCSs yielding potentially complex signalling landscapes.

Item Type:	Journal Article
Publication:	BIOCHEMICAL JOURNAL
Publisher:	PORTLAND PRESS LTD
Additional Information:	Copy right for this article belongs to the PORTLAND PRESS LTD, CHARLES DARWIN HOUSE, 12 ROGER STREET, LONDON WC1N 2JU, ENGLAND
Keywords:	cross-talk; histidine kinase; interactome; response regulator; systems biology; two-component system
Department/Centre:	Division of Biological Sciences > Molecular Reproduction, Development & Genetics Division of Mechanical Sciences > Chemical Engineering
Date Deposited:	09 Oct 2015 05:05
Last Modified:	06 Oct 2018 12:59
URI:	http://eprints.iisc.ac.in/id/eprint/52515

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