Modified staphylococcal peptidoglycan cross-bridge

The staphylococcal peptidoglycan cross-bridge is a specialized structural element of the bacterial cell wall that provides the necessary tensile strength to withstand high internal osmotic pressure. In Staphylococcus aureus, this bridge typically consists of five glycine residues (pentaglycine) that link adjacent glycan strands via their peptide side chains (PubMed: 18485611). Modifications to this structure, such as the substitution of glycine with L-serine or the shortening of the bridge length, are frequently observed in resistant strains and are mediated by enzymes like FemA, FemB, and Lif (PubMed: 11073907, PubMed: 10449223). These modified cross-bridges are the direct targets of certain antimicrobial agents, most notably lysostaphin, a glycylglycine endopeptidase that specifically cleaves the glycine bonds (PubMed: 15138253). Because these bridges are unique to staphylococci and essential for viability, they represent a highly specific target for the development of narrow-spectrum enzybiotics. Targeting the modification process or the modified bridge itself is a strategic approach to overcoming multi-drug resistance, including methicillin and glycopeptide resistance. However, therapeutic challenges include the potential for further bacterial evolution to alter bridge composition and the immunogenicity of protein-based drugs targeting these structures.

Other names

Pentaglycine cross-bridgePeptidoglycan interpeptide bridgeStaphylococcal Gly5 bridgeSerine-modified peptidoglycan bridgeFem-mediated cross-link

Endopeptidase-mediated cleavage of the glycyl-glycine bonds within the cross-bridge, leading to cell wall degradation and osmotic lysis (PubMed: 15138253).