Two-Component Regulatory Systems in Microbial Pathogenesis

Bacteria would adapt to ever-changing multifaceted environments. Two-component systems (TCSs) are predominantly used by bacteria to respond to environmental cues. TCSs regulate the expression of genes involved in quorum sensing, biofilm formation, cell growth and division, acid tolerance, spore formation, virulence, drug resistance, and nitrogen fixation. TCSs are composed of sensor (histidine kinase; HK—membrane-bound homodimeric protein) and a cognate response regulator (RR) which on phosphorylation by HK is converted into active DNA binding form and alters gene expression. TCSs are used by virulent bacteria to control the expression of virulence factors. The aerobic respiration control (Arc) TCS plays a role in anaerobic to aerobic shift by sensing oxygen availability or consumption. Evolutionary dynamics explains a dramatic increase in the number of TCSs within many bacterial genomes through gene duplication and the subsequent divergence, enabling the microbes to sense and respond to various environmental stimuli. Bacterial TCSs are promising targets for antimicrobial therapy.