Cell surface display of bacterial proteins

点击翻译按钮获取中文摘要

The proteins exposed at the cell surface of bacteria play a pivotal role in a multitude of fundamental processes such as cell growth and division. In pathogens, surface proteins promote host invasion and later during infection, evasion from the host immune response. Most surface proteins are anchored to a scaffold molecule called peptidoglycan, an essential component of the bacterial envelope. Peptidoglycan is a bag-shaped giant molecule surrounding the cell that made plays a protective role. Its synthesis is unique to bacteria and represents the target of the most important antibiotics ever discovered such as penicillin. To date, a plethora of surface proteins has been described but how they interact with the bacterial envelope remain poorly understood. We have recently described the molecular basis for peptidoglycan recognition by a ubiquitous protein domain called LysM in vitro using synthetic ligands. We are now ready to take the next step to actually understand how LysM proteins bind to the complex peptidoglycan molecule in live bacteria and are targeted to specific subcellular localizations. To achieve this aim, we will use a multidisciplinary approach combining bacterial genetics, state-of-the-art microscopy and biophysics. Binding of LysM domains to the PG molecule represents a key bacterial mechanism for controlling the location, synthesis, degradation and decoration of cell wall features. The understanding generated by this project will give us the tools to dissect how bacteria grow, divide and interact with their environment, to develop new therapeutic strategies, and to learn how to apply synthetic biology to bacterial cell walls.