Grant: Project Grant

Bacteria are surrounded by envelopes that are responsible for cell shape and size. Bacterial cell shape and size are important for the organization of intracellular processes, for multicellular interactions, and for infection. The cell envelope also protects bacteria from the environment. The envelope component physically responsible for cell shape and envelope integrity is the peptidoglycan cell wall, a single molecule that surrounds the cell. During growth the cell wall must be enzymatically cut, and new material must be inserted. The enzymes responsible for these processes thus determine cell shape during growth. Not surprisingly, the cell wall is a major target for antibiotics including penicillin. Many of the enzymes and proteins responsible for cell-wall remodeling are known. However, we still lack a fundamental understanding of how enzyme activity leads to macroscopic cell shape and envelope integrity. Here I propose to investigate the spatial organization and activity of different processes that remodel the cell wall, focusing on the process of cell elongation in the Gram-negative bacterium Escherichia coli. As a major tool, we will use high- precision live-cell microscopy, which is paired with well-defined perturbations of the cell envelope and of different enzymes and proteins. Our findings then inform mathematical models of cell-shape control. Our insights will lead to a better understanding of cell-wall organization and cell shape in Gram-negative bacteria. Since the cell wall is a major target for antibiotic therapy, this project will also inform the search for new strategies to fight the emergence of antimicrobial resistance.