Bacterial cell wall synthesis and recycling: new antimicrobial targets and vaccine development

Almost all bacteria have peptidoglycan (PG) components that are essential for virulence and are absent in humans, making them a top-priority target for antibiotics and vaccines. The rise of multidrug-resistant bacteria (MRB) necessitates urgent expansion of our arsenal of inhibitors targeting the PG cell wall. This review addresses our understanding of PG biosynthesis and recycling processes, emphasizing the need to identify novel target proteins and redesign existing PG-targeted antimicrobial peptides. Building on our understanding of cell wall biochemistry and biogenesis derived from Escherichia coli, we also aim to compare and elucidate the cell wall processes in other pathogens, such as Acinetobacter baumannii and Salmonella Typhimurium, where knowledge remains incomplete. We cover in detail the distinct roles of PG-related proteins in Gram-negative bacteria, strategies to block PG biosynthesis/recycling pathways, and their potential as novel antibiotic targets to address the growing challenge of antibiotic resistance. Finally, we review the application of rigorous immuno-informatics analysis and several immune filters to construct epitope-specific vaccines displaying PG-related proteins on the surface of outer membrane vesicles (OMVs), aiming to combat MRB proliferation.