Cross‐talk suppression between the CpxA–CpxR and EnvZ–OmpR two‐component systems in E. coli

SummaryMany bacteria possess large numbers of two‐component signalling systems, which are composed of histidine kinase‐response regulator pairs. The high level of sequence similarity between some systems raises the possibility of undesired cross‐talk between a histidine kinase and a non‐cognate response regulator. Although molecular specificity ensures that phospho‐transfer occurs primarily between correct partners, even a low level of inappropriate cross‐talk could lead to unacceptable levels of noise or interference in signal transduction. To explore mechanisms that provide insulation against such interference, we have examined cross‐talk between the histidine kinase CpxA and non‐cognate response regulator OmpR in Escherichia coli. Our results show that there are two mechanisms that suppress cross‐talk between these two proteins, which depend on the corresponding cognate partners CpxR and EnvZ and on the bifunctional nature of the histidine kinases CpxA and EnvZ. When cross‐talk is detectable, we find it is independent of CpxA stimulus. We also show that cross‐talk suppression leads to mutational robustness, i.e. it masks the effects of mutations that would otherwise lead to increased cross‐talk. The mechanisms that provide insulation against interference described here may be applicable to many other two‐component systems.