Bacterial two-component regulatory system (TCS) (TCS)

Bacterial two-component regulatory systems (TCS) are the primary signal transduction pathways used by bacteria to sense and respond to environmental stimuli (MDPI, 2020; Wikipedia). A prototypical TCS consists of a membrane-bound sensor histidine kinase (HK) and a cognate cytoplasmic response regulator (RR) (Frontiers in Microbiology, 2017). Upon activation by an external signal, the HK autophosphorylates at a conserved histidine residue and subsequently transfers the phosphate group to an aspartate residue on the RR (MDPI, 2020). The phosphorylated RR then typically functions as a transcription factor to modulate the expression of target genes involved in virulence, antibiotic resistance, biofilm formation, and essential metabolic processes (PNAS, 2000; Frontiers in Microbiology, 2017). Because TCS are ubiquitous in bacteria but absent in mammalian cells, they represent a highly attractive target for the development of novel antimicrobial agents (MDPI, 2020; PNAS, 2000). Targeting these systems can either directly inhibit bacterial growth or attenuate the pathogen's ability to cause disease and resist existing antibiotics, offering a promising strategy to combat multi-drug resistant infections (MDPI, 2020; Frontiers in Microbiology, 2017).

Other names

Two-component systemTwo-component signal transduction systemTCSTSHis-Asp phosphorelayHistidine kinase/Response regulator system

Inhibition of histidine kinase autophosphorylation, inhibition of phosphoryl transfer from histidine kinase to response regulator, and inhibition of response regulator DNA binding (MDPI, 2020; PNAS, 2000).