Deconstructing energised associations that build and maintain the Gram-negative Bacterial Cell Envelope

Antibiotic resistance in bacteria is a major threat to human health. A significant feature of resistance is the exclusion of molecules by the protective bacterial cell envelope. A multitude of infections including, pneumonia, urinary tract infections, meningitis, and wound infections are caused by Gram-negative bacteria, which have a particularly complex cell envelope structure. How Gram-negative bacteria coordinate septation of their three-layered cell envelope is poorly understood. The aim of this research is to address this question by determining how protein complexes that span the envelope layers assemble and console both biological function and preservation of structure. The interactions between proteins associated with the different envelope layers bestows a link between the outer and inner layers of the envelope. These protein complexes are often dynamic, transducing energy across the envelope to drive biological processes. To ensure this functionality remains intact following cell division membrane invagination and peptidoglycan synthesis must be coordinated. This proposal will use combination of microbiological, structural, biophysical, and biochemical techniques to determine the molecular mechanisms that allow energised coordination of cell envelope layers during division. The information gained from these studies can be exploited to combat antimicrobial resistance identifying novel targets for disruption of bacterial cell division.