EvgS/EvgA, the unorthodox two-component system regulating bacterial multiple resistance

Two-component systems (TCSs) widely exist in bacteria and assist bacteria in adjusting behaviors to adapt to environmental changes after sensing environmental signals and transducing information into cells. As a member of TCSs in Escherichia coli, after sensing signals, EvgS/EvgA mainly induces multiple resistances, such as acid and multidrug resistance, and increases bacterial adherence. Notably, the EvgS is one of the five unorthodox sensors in E. coli, which has an internal phosphorelay based on the structure with extra domains different from other orthodox sensors. Here, we summarize research on EvgS and EvgA published since 1994. This review includes comprehensive knowledge of EvgS/EvgA and focuses on the EvgS structure and the multiple resistance conferred by EvgS/EvgA. Furthermore, we discuss the unsolved questions of EvgS/EvgA and propose assumptions and inferences on the EvgS structure and the EvgS/EvgA function.IMPORTANCEEvgS/EvgA, one of the five unorthodox two-component systems in Escherichia coli, plays an essential role in adjusting bacterial behaviors to adapt to the changing environment. Multiple resistance regulated by EvgS/EvgA endows bacteria to survive in adverse conditions such as acidic pH, multidrug, and heat. In this minireview, we summarize the specific structures and regulation mechanisms of EvgS/EvgA and its multiple resistance. By discussing several unresolved issues and proposing our speculations, this review will be helpful and enlightening for future directions about EvgS/EvgA. EvgS/EvgA, one of the five unorthodox two-component systems in Escherichia coli, plays an essential role in adjusting bacterial behaviors to adapt to the changing environment. Multiple resistance regulated by EvgS/EvgA endows bacteria to survive in adverse conditions such as acidic pH, multidrug, and heat. In this minireview, we summarize the specific structures and regulation mechanisms of EvgS/EvgA and its multiple resistance. By discussing several unresolved issues and proposing our speculations, this review will be helpful and enlightening for future directions about EvgS/EvgA.