Glycine-containing peptidoglycan cross-link

Glycine-containing peptidoglycan cross-links are essential structural motifs in the cell walls of various Gram-positive bacteria, particularly within the genus Staphylococcus [1, 3]. These interpeptide bridges, which often consist of a pentaglycine chain, connect the L-lysine of one stem peptide to the D-alanine of another, providing the mechanical strength required to withstand high internal osmotic pressure [1, 3]. While the pentaglycine bridge is the hallmark of Staphylococcus aureus, similar glycine-rich bridges are found in non-S. aureus species such as S. epidermidis, S. simulans, and S. saprophyticus, although they may occasionally incorporate L-serine or L-alanine [1, 4]. These cross-links are the specific substrate for glycyl-glycine endopeptidases like lysostaphin and ALE-1, which cleave the peptide bonds between glycine residues [2, 4]. The targeted hydrolysis of these bridges leads to the rapid disintegration of the peptidoglycan network, resulting in bacterial lysis [2]. Consequently, these cross-links represent a vulnerable therapeutic target for treating infections caused by coagulase-negative staphylococci, which are increasingly associated with biofilm-mediated infections on medical implants [2, 3].

Other names

Peptidoglycan interpeptide bridgeGlycine-rich cross-bridgePentaglycine bridgeGlycyl-glycine cross-linkStaphylococcal interpeptide bridge

Hydrolysis of glycyl-glycine peptide bonds within the interpeptide bridge, leading to cell wall degradation and osmotic lysis.