Signal integration in bacterial two-component regulatory systems

Two-component systems (TCSs) and phosphorelays are key mediators of bacterial signal transduction. The signals activating these systems promote the phosphorylated state of a response regulator, which is generally the form that carries out specific functions such as binding to DNA and catalysis of biochemical reactions. An emerging class of proteins-termed TCS connectors modulate the output of TCSs by affecting the phosphorylation state of response regulators. TCS connectors use different mechanisms of action for signal integration, as well as in the coordination and fine-tuning of cellular processes. Present in both Gram-positive and Gram-negative bacteria, TCS connectors are critical for a variety of physiological functions including sporulation, competence, antibiotic resistance, and the transition to stationary phase.