Practice question

Crosslinking between glycan strands in many Gram-positive pathogens involves pentaglycine bridge characteristic of Staphylococcus aureus, intensively studied because it influences vancomycin sensitivity. After polymerization, tetrapeptide side chains protrude from MurNAc. In S. aureus, FemXAB family nonribosomal peptidyl transferases add glycine residues one by one to epsilon amino group of L-lysine at position three, using glycyl-tRNA as donor, generating pentaglycine. This flexible extension then becomes substrate for transpeptidase that links glycine terminal to D-alanine of neighboring stem, creating pentaglycine cross-bridge. Composition varies: Streptococcus pneumoniae uses dipeptide L-Ala-L-Ala, Enterococcus uses L-Ala-L-Ala or L-Ala-L-Ser. Glycine as smallest amino acid provides flexibility facilitating long crosslinks, increasing cell wall thickness and resistance to lysozyme. Interpeptide bridges containing alanine, serine, or proline also occur, but glycine dominance in this species is textbook example of how nonribosomal amino acid incorporation shapes wall architecture and antibiotic resistance through Fem-mediated bridging and altered penicillin-binding protein 2a affinity. The pentaglycine bridge length influences susceptibility to lysostaphin, an endopeptidase from Staphylococcus simulans that specifically cleaves Gly-Gly bonds, widely used in laboratory to lyse staphylococci, and to host immunity protein FemX-mediated resistance mechanisms that replace glycine with serine in some methicillin-resistant isolates, altering bridge flexibility and vancomycin binding.