The Two Component Signaling Networks of Mycobacterium tuberculosis Displays Extensive Crosstalk 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 M. tuberculosis (Mtb), we mapped the complete interactome of the Mtb TCSs using phosphotransfer profiling. Surprisingly, we found extensive crosstalk among the Mtb TCSs, significantly more than that in the TCSs in E. coli or Caulobacter crescentus, thereby offering an alternate to specificity paradigm in TCS signaling. Nearly half the interactions we detected were significant, novel cross-interactions, unraveling a potentially complex signaling landscape. We classified the TCSs into specific ‘one-to-one’ and promiscuous ‘one-to-many’ and ‘many-to-one’ circuits. Using mathematical modeling, we deduced that the promiscuous signaling observed can explain several currently confounding observations about Mtb TCSs. Our findings suggest an alternative paradigm of bacterial signaling with significant crosstalk between TCSs yielding potentially complex signaling landscapes.
Source: BJ Signal - Category: Biochemistry Authors: Tags: BJ Signal Source Type: research