Escherichia coli and related bacteria employ multi-step phosphorelays to sense intra- and extra-cellular environmental signals and to modulate diverse cellular processes. However, the significance of the multiple phosphoryl transfer steps that characterize these systems remains poorly understood. As part of our long- term goal to understand the interplay between the various signal transduction systems that bacteria employ to adapt to diverse environmental conditions, this proposal will explore several of these systems that are particularly tractable, due to well-established inputs and/or outputs, and that play critically important roles in E. coli physiology. The primary focus will be on two phosphorelays that are important for the transition to anaerobiosis, Arc and Tor, as well as a phosphohistidine phosphatase that modulates the nitrogen-related phosphotransferase system. Progress in understanding these networks will provide new insights into both the mechanisms enabling infections by pathogens and the maintenance of a healthy microbiota in host niches. The results may ultimately lead to the development of novel antibiotics or treatment regimens, as well as strategies for manipulating the microbiomes to maintain the health of the host.
This project will explore the underlying mechanisms controlling a class of pathways that are critical for E. coli and related bacteria to adapt to changes in the environment, such as fluctuations in oxygen availability or extracellular potassium. The insights into these systems and into the bacterial strategies for surviving changes in the environment that will emerge from this research may lead to novel therapies for controlling bacterial infections and maintaining healthy microbiomes.