Modulators of The Bacterial Two-component Systems Involved in Envelope Stress, Transport, and Virulence

The two-component systems (TCSs) allow bacteria to respond appropriately to constant changes in the environment in which they live. A typical TCS has two core regulatory proteins: a sensor kinase (SK) that receives the environmental signal and a cognate response regulator (RR), which is often a transcription factor. Many SKs are multifunctional, with abilities to autophosphorylate a conserved histidine residue, transfer the phosphoryl group to a conserved aspartate residue of the corresponding RR, and strip the phosphoryl group from the RR. However, in more complex systems, additional steps of intra- and/or intermolecular phosphorelay events precede phosphorylation of RR. Environmental and chemical signals influence any one of the three SK activities to affect the biochemical output to RR, either directly or indirectly via the assistance of an accessory factor or modulator. This chapter focuses on the envelope-localized modulators, some of which also serve to bridge two different TCSs.