Peptidoglycan pentaglycine cross-bridge (Staphylococcus aureus) (Pentaglycine bridge)

The peptidoglycan pentaglycine cross-bridge is a critical structural component of the Staphylococcus aureus cell wall, distinguishing it from many other bacterial species [5]. It consists of five glycine residues that link the L-lysine of one stem peptide to the D-alanyl-D-alanine (D-Ala-D-Ala) terminus of an adjacent stem peptide during peptidoglycan biosynthesis [5]. This cross-linking provides the mechanical strength and rigidity necessary for the bacterium to withstand high internal osmotic pressure [5]. The D-Ala-D-Ala motif within this context is the primary target for glycopeptide antibiotics like vancomycin, which bind to the terminus and sterically hinder the transpeptidation and transglycosylation reactions [1, 4]. Additionally, the pentaglycine bridge itself is the specific target of the endopeptidase lysostaphin, which cleaves the glycine-glycine bonds, leading to rapid bacterial lysis [2]. Because this structure is essential for bacterial survival and absent in eukaryotic cells, it represents a highly effective target for antimicrobial therapy against staphylococcal infections, including methicillin-resistant S. aureus (MRSA) [3, 4].

Other names

Pentaglycine interpeptide bridgeGly5 cross-bridgeStaphylococcal pentaglycine bridgePeptidoglycan cross-link

Glycopeptide antibiotics bind to the D-Ala-D-Ala terminus of the peptidoglycan stem peptide, sterically hindering the transpeptidation and transglycosylation steps of cell wall synthesis [1, 4]. Alternatively, the endopeptidase lysostaphin targets the pentaglycine cross-bridge directly, cleaving the glycine-glycine bonds to cause bacterial cell lysis [2].