Cell wall hydrolases of Escherichia coli

SUMMARY Bacterial cell walls are made up of peptidoglycan (PG), a primary load-bearing layer that forms a protective exoskeleton around the cytoplasmic membrane. PG is a heteropolymer composed of glycan chains attached to short peptides that are crosslinked to each other, forming a mesh-like macromolecule that prevents osmotic lysis of the cell. Far from being a static exoskeleton, PG is a dynamic living polymer that undergoes continuous synthesis, expansion, remodeling, and turnover throughout the bacterial cell cycle. Central to the dynamic nature of PG is a finely tuned balance between two seemingly opposite processes—synthesis and hydrolysis. The PG synthases, which are essential for bacterial viability, have long been recognized as excellent drug targets and have therefore been studied extensively for decades. On the other hand, the significance of PG hydrolysis in diverse fundamental PG processes has become increasingly evident in recent years. Bacteria encode several highly conserved PG hydrolases with distinct substrate specificities that contribute to critical cellular processes, including cell wall expansion during growth, cell division, remodeling, and recycling, as well as predation and pathogenesis. Consequently, PG hydrolases represent promising targets for the development of novel antibacterial therapeutics. This review provides a comprehensive overview of the classification, physiological functions, and regulatory mechanisms governing the PG hydrolases in the model organism Escherichia coli and highlights parallels among related taxa across the bacterial kingdom.