peptidoglycan

Peptidoglycan, also known as murein, is the polymer that forms the cell wall of most bacteria. It provides mechanical strength, helps determine cell shape, and protects against osmotic pressure.

Structure and variation: Peptidoglycan consists of long chains of repeating disaccharide units made of N-acetylglucosamine (GlcNAc) and N-acetylmuramic acid (MurNAc) linked by β-(1,4) glycosidic bonds. Each MurNAc carries a short peptide stem; these peptides are cross-linked between adjacent glycan strands to create a rigid, mesh-like lattice. Some bacteria use peptide bridges (for example, pentaglycine in Staphylococcus aureus) to connect cross-links. The overall thickness and composition of the peptidoglycan layer differ between Gram-positive bacteria (thicker layer) and Gram-negative bacteria (thinner layer enclosed by an outer membrane).

Biosynthesis and remodeling: Synthesis begins in the cytoplasm with UDP-MurNAc-pentapeptide, which is linked to a lipid carrier (bactoprenol). The lipid-linked precursor is flipped across the cytoplasmic membrane, the glycan strands are extended by glycosyltransferases, and the peptide side chains are cross-linked by transpeptidases, often called penicillin-binding proteins. The cell wall is continuously remodeled by autolysins during growth and division.

Clinical relevance: Peptidoglycan is a key antibiotic target because it is absent in human cells. Beta-lactam antibiotics inhibit transpeptidation, preventing cross-linking, while glycopeptides like vancomycin block incorporation of the terminal D-Ala-D-Ala units. Lysozyme, an innate immune enzyme, cleaves the GlcNAc-MurNAc linkage, weakening the cell wall. The structure and synthesis of peptidoglycan influence bacterial survival and antibiotic susceptibility.