Peptidoglycan biosynthesis and remodeling revisited

The bacterial peptidoglycan layer forms a complex mesh-like structure that surrounds the cell, imparting rigidity to withstand cytoplasmic turgor and the ability to tolerate stress. As peptidoglycan has been the target of numerous clinically successful antimicrobials such as penicillin, the biosynthesis, remodeling and recycling of this polymer has been the subject of much interest. Herein, we review recent advances in the understanding of peptidoglycan biosynthesis and remodeling in a variety of different organisms. In order for bacterial cells to grow and divide, remodeling of cross-linked peptidoglycan is essential hence, we also summarize the activity of important peptidoglycan hydrolases and how their functions differ in various species. There is a growing body of evidence highlighting complex regulatory mechanisms for peptidoglycan metabolism including protein interactions, phosphorylation and protein degradation and we summarize key recent findings in this regard. Finally, we provide an overview of peptidoglycan recycling and how components of this pathway mediate resistance to drugs. In the face of growing antimicrobial resistance, these recent advances are expected to uncover new drug targets in peptidoglycan metabolism, which can be used to develop novel therapies.