Local and global regulation of bacterial growth

Bacteria impact human health in myriad ways, including as infectious agents and beneficial members of our microbiota. As single-celled organisms, bacteria must be able to reproduce through successive rounds of cell division to generate a population of cells that can cause infection or act as beneficial commensals. Moreover, bacterial survival requires an ability to sense and respond to changes in their environment, including stresses like antibiotics. Our proposed work centers on these two fundamental aspects of bacterial life – replication and adaptation – with a focus on the role of the cell envelope in these processes. We leverage the dimorphic alphaproteobacterium Caulobacter crescentus for this research. In our first research area, we will continue to build on our recent work delineating a pathway the links chromosome segregation to the activation of peptidoglycan cell wall synthesis that drives constriction during division. We will use a diverse array of approaches including genetics, biochemistry, and advanced imaging to establish the mechanisms that allow Caulobacter to ensure genome integrity throughout the process of cell division. In the second research area, we will build on a framework we recently established to understand the composition and function of envelope components known as osmoregulated periplasmic glucans (OPGs) in ensuring envelope integrity and promoting morphogenesis and survival. OPGs are essential in Caulobacter, and their loss has both direct effects on morphology and indirect effects through activation of the CenKR two-component system that regulates envelope homeostasis. We will leverage genetics, biochemistry, advanced imaging, and transcriptomics to understand how OPGs are metabolized, how they promote envelope integrity and morphogenesis, and how they integrate with the CenKR two-component system. Collectively our work will advance our understanding of key aspects of bacterial physiology and replication, and will promote our ability to combat antibiotic resistance through identification of new therapeutic targets.