Pentaglycine cross-bridge

The pentaglycine cross-bridge is a distinctive structural component of the Staphylococcus aureus cell wall, composed of five glycine residues that link the epsilon-amino group of L-lysine in one peptidoglycan stem peptide to the D-alanine of another (Schneewind et al., 1995, PubMed: 7616570). This specific cross-linking motif is essential for the mechanical stability and integrity of the staphylococcal cell wall, allowing the bacterium to survive high internal osmotic pressures (Bastos et al., 2010, PubMed: 20660094). Unlike many other bacteria that use direct cross-links or shorter bridges, the length and composition of the pentaglycine bridge are unique to S. aureus and closely related species. This uniqueness makes it an ideal target for highly specific antimicrobial therapies, most notably the enzyme lysostaphin, which acts as a glycylglycine endopeptidase to cleave the bridge (Sabala et al., 2014, PubMed: 24513112). Cleavage of these bridges results in the rapid loss of cell wall integrity and subsequent bacterial lysis. Additionally, the biosynthetic enzymes responsible for bridge formation, such as FemA, FemB, and FemX, are considered significant targets for overcoming antibiotic resistance, particularly in methicillin-resistant S. aureus (MRSA) strains (Rohrer et al., 1999, PubMed: 10411749).

Other names

Pentaglycine interpeptide bridge(Gly)5 bridgeStaphylococcal pentaglycine bridgePentaglycine cross-link

Lysostaphin acts as a glycylglycine endopeptidase that specifically cleaves the glycyl-glycine bonds within the pentaglycine cross-bridge, leading to rapid cell wall degradation and bacterial lysis (Bastos et al., 2010).