YpdAB and BtsRS: Interconnected Signaling Networks with Pyruvate and Acid Sensing Functions in Uropathogenic Escherichia coli

Abstract

Two-component systems (TCSs) are an important class of signal transduction systems in bacteria. TCSs can control many aspects of bacterial physiology and are vital intermediaries that allow a bacterium to monitor its environment, to maintain intracellular homeostasis, and to respond to the ever changing needs of bacterial life. Notably, TCSs do not exist in humans, which in conjunction with their many important functions makes them potentially useful targets for future antimicrobial therapeutics. TCSs function via the activation of a membrane-embedded sensor kinase which then activate a specific cognate response regulator protein. However, although canonically these sensor-regulator interactions were viewed as strictly insulated events, recent work in our laboratory and in the laboratory of others has shown that TCSs may be capable of functioning together in complex signaling networks, and that the proper regulation of these networks has a substantial impact on pathogen fitness. Here we demonstrate the interconnected nature of the YpdAB and BtsRS TCSs in uropathogenic Escherichia coli (UPEC). Additionally, we investigate the activating stimuli of YpdAB and BtsRS, acidic stress and pyruvate respectively, explore the potential roles of these stimuli in UPEC pathogenesis, and propose future experiments to investigate these systems further.