Manipulation of Bacterial Signaling Using Engineered Histidine Kinases.

Two-component systems allow bacteria to respond to changes in environmental or cytosolic conditions through autophosphorylation of a histidine kinase (HK) and subsequent transfer of the phosphate group to its downstream cognate response regulator (RR). The RR then elicits a cellular response, commonly through regulation of transcription. Engineering two-component system signaling networks provides a strategy to study bacterial signaling mechanisms related to bacterial cell survival, symbiosis, and virulence, and to develop sensory devices in synthetic biology. Here we focus on the principles for engineering the HK to identify unknown signal inputs, test signal transmission mechanisms, design small molecule sensors, and rewire two-component signaling networks.