Molecular mechanisms controlling stress responses and cell adhesion in bacteria

Project Summary/Abstract We seek to understand molecular mechanisms that enable bacteria to survive in complex, dynamic environments, including mammalian hosts. The research program proposed here will build on advances made by our team in the previous term of this award, which have centered on two themes: 1) signaling mechanisms that support cell survival during stress, 2) regulatory mechanisms that mediate bacterial cell interactions with abiotic surfaces and with bacteriophage. Over the next five years, we will utilize an interdisciplinary set of genetic, biochemical, and structural approaches to study these processes on multiple scales, from the systems level to the level of molecular structure. The data that emerge from our studies will enhance understanding of processes that allow bacteria to grow and survive in complex environments and will inform new concepts in gene regulation and cell envelope biology. More specifically, this project will provide the scientific community with an integrative understanding of sensory transduction mechanisms in bacteria and will lead to improved understanding of the molecular mechanisms underlying biogenesis of the complex structure known as the envelope, which separates the tightly controlled activities in the cytoplasm from the outside world. In this next period of the award, we further propose to extend our studies to include mechanisms by which XRE family transcription factors – which are known regulators of envelope polysaccharide biosynthesis - influence host- phage dynamics. Sensory transduction proteins and cell envelope polysaccharides are well-defined virulence determinants in many bacterial pathogens. Thus, our work has the potential to inform new therapeutic routes to control certain bacterial infections.