The two-component signalling networks of Mycobacterium tuberculosis display extensive cross-talk in vitro.
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 cross-talk 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.
Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore, India.
Ruchi
R
Agrawal
Department of Chemical Engineering, Indian Institute of Science, Bangalore, India.
Akancha
A
Pandey
Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore, India.
Mayooreshwar P
MP
Rajankar
Department of Chemical Engineering, Indian Institute of Science, Bangalore, India Bioengineering Program, Indian Institute of Science, Bangalore, India.
Narendra M
NM
Dixit
Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore, India Bioengineering Program, Indian Institute of Science, Bangalore, India deepak@mrdg.iisc.ernet.in.
Deepak K
DK
Saini
D001426:Bacterial Proteins / Q000378:metabolism*; D008954:Models, Biological; D009169:Mycobacterium tuberculosis / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
D001426:Bacterial Proteins
cross-talk; histidine kinase; interactome; response regulator; systems biology; two-component system