The PhoPQ two-component regulatory system as an important regulator of bacterial stress response.

Two-component regulatory systems (TCSs) are fundamental regulatory mechanisms that enable bacteria to detect and respond to a wide range of environmental signals. Each TCS typically consists of two proteins: a membrane-associated histidine kinase that acts as a sensor, and a cytoplasmic response regulator that mediates transcriptional changes. This design allows TCSs to enable bacteria to precisely regulate their physiology and adapt to changing environmental conditions. Among these systems, PhoPQ is one of the better characterised examples, particularly in Gram-negative pathogens. The PhoPQ system responds to environmental signals such as cationic antimicrobial peptides, low pH, and changes in metal ion concentrations (e.g., Mg²⁺, Ca²⁺, Fe³⁺). Activation of PhoPQ initiates the regulation of many downstream genes, including those responsible for lipid A modification, which in turn contributes to bacterial resistance to polymyxin B. A growing body of evidence points to the key role of PhoPQ in the virulence and survival of many Gram-negative bacteria. This makes PhoPQ not only an important element of bacterial pathogenicity, but also a promising therapeutic target for the development of new pharmacological strategies.