Pentaglycine bridge of staphylococcal peptidoglycan

The pentaglycine bridge of staphylococcal peptidoglycan is a specific interpeptide cross-link consisting of five glycine residues that covalently connects peptide stems within the peptidoglycan of *Staphylococcus aureus* and related staphylococci. This bridge forms the basis for high levels of cross-linking, providing the cell wall with essential mechanical strength and rigidity to withstand osmotic pressure[2][3][7]. The biosynthesis of the pentaglycine bridge is mediated by the FemXAB family of proteins, with FemX, FemA, and FemB sequentially adding glycine residues to the lysine residue at the third position of the peptidoglycan stem peptide[7]. The presence of the pentaglycine bridge is critical for the survival of *S. aureus*; depletion or disruption of this structure results in loss of cell wall integrity and rapid cell lysis[7]. Drugs such as β-lactam and glycopeptide antibiotics exploit this essential cross-link by inhibiting enzymes that catalyze bridge formation or subsequent cross-linking, leading to cell death[2][7]. Alterations in the structure or biosynthesis of the pentaglycine bridge can modulate antibiotic resistance, most notably in methicillin-resistant *S. aureus* (MRSA), where alternative penicillin-binding proteins allow for continued cell wall synthesis despite antibiotic presence[1][7]. This target is considered druggable, as inhibition of the bridge's formation renders the bacterium nonviable, but it is not a single protein or receptor—it is a unique, essential structural moiety of the bacterial cell wall.

Other names

Peptidoglycan pentaglycine interpeptide bridgeStaphylococcal pentaglycine cross-bridgeGly5 interpeptide bridge

Inhibition of pentaglycine bridge formation prevents proper cross-linking of peptidoglycan, leading to cell lysis (β-lactam and glycopeptide antibiotics)