Peptidoglycan pentaglycine bridge

The peptidoglycan pentaglycine bridge is a critical structural element found in the cell wall of certain Gram-positive bacteria, most notably Staphylococcus aureus (S. aureus) (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3122230/). It consists of five glycine residues that form a cross-link between the L-lysine of one peptidoglycan stem peptide and the D-alanine of an adjacent one, providing the cell wall with essential mechanical strength and rigidity (https://pubmed.ncbi.nlm.nih.gov/11073907/). This bridge is synthesized by the Fem (factor essential for methicillin resistance) family of proteins, which sequentially add glycine residues to the lipid-linked peptidoglycan precursors (https://journals.asm.org/doi/10.1128/jb.182.23.6724-6731.2000). Because this specific interpeptide bridge is unique to certain bacteria and absent in human cells, it serves as an ideal target for highly selective antimicrobial agents (https://www.nature.com/articles/s41598-017-15509-3). Lysostaphin, a potent glycylglycine endopeptidase, specifically targets and cleaves these glycine-glycine bonds, resulting in the rapid lysis of the bacterial cell (https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/lysostaphin). Targeting the pentaglycine bridge is a significant area of research for developing treatments against multidrug-resistant pathogens, including methicillin-resistant S. aureus (MRSA) (https://www.frontiersin.org/articles/10.3389/fmicb.2019.02608/full).

Other names

Pentaglycine interpeptide bridgePentaglycine cross-linkGly5 bridgeStaphylococcal pentaglycine bridgePentaglycine bridge

Enzymatic cleavage of glycyl-glycine bonds within the interpeptide bridge, leading to loss of cell wall integrity and bacterial lysis (https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/lysostaphin).