- Peptidoglycan, also known as murein, is a complex polymer of sugars and amino acids that forms the rigid cell wall of most bacteria, providing structural integrity and shape while protecting against osmotic lysis.
- It is composed of linear chains of alternating N-acetylglucosamine (GlcNAc) and N-acetylmuramic acid (MurNAc), connected by β-(1→4) glycosidic bonds. Attached to the MurNAc residues are short peptide chains, typically consisting of four to five amino acids, which can cross-link with peptides from adjacent strands. This mesh-like network creates a strong but flexible structure that enables bacterial cells to withstand high internal turgor pressure.
- The structure of peptidoglycan varies between Gram-positive and Gram-negative bacteria, reflecting their different cell envelope architectures. In Gram-positive bacteria, peptidoglycan forms a thick, multilayered structure (20–80 nm thick) that accounts for much of the cell wall mass, often containing additional polymers such as teichoic acids. In Gram-negative bacteria, peptidoglycan is relatively thin (2–7 nm) and located within the periplasmic space, sandwiched between the inner cytoplasmic membrane and the outer membrane. Despite being thinner, the Gram-negative peptidoglycan layer plays a crucial role in maintaining cell shape and anchoring proteins in the periplasm.
- Biologically, peptidoglycan is essential for bacterial growth, division, and survival. During cell division, specialized enzymes such as autolysins and transglycosylases remodel the peptidoglycan layer, while penicillin-binding proteins (PBPs) catalyze the cross-linking of peptide side chains, ensuring stability of the new cell wall material. Because of its vital role, peptidoglycan biosynthesis is one of the most important targets for antibiotics. For example, β-lactam antibiotics (penicillins, cephalosporins) inhibit PBPs and block cross-linking, leading to cell lysis, while glycopeptides such as vancomycin bind to peptide precursors and prevent incorporation into the cell wall. This makes peptidoglycan a focal point in antimicrobial therapy and a major driver of research into antibiotic resistance mechanisms.
- Beyond its structural role, peptidoglycan also plays a key part in host–pathogen interactions. Fragments of peptidoglycan released during bacterial growth or lysis can be recognized by the host immune system through pattern recognition receptors (PRRs) such as NOD1 and NOD2, triggering innate immune responses and inflammation. These interactions are important for host defense but can also contribute to pathologies such as chronic inflammation, sepsis, or autoimmune disorders when dysregulated.
- Peptidoglycan has also been a tool in microbiology and biotechnology. Its structural differences between Gram-positive and Gram-negative bacteria form the basis of the Gram staining technique, a cornerstone in bacterial classification. Additionally, modifications of peptidoglycan (e.g., O-acetylation, amidation, or glycan substitutions) can influence bacterial virulence, resistance to lysozyme (an antimicrobial enzyme that cleaves β-(1→4) linkages), and adaptation to different environments.
- From an evolutionary perspective, peptidoglycan is thought to be an ancient feature of bacteria, though not universal. Some groups such as mycoplasmas lack peptidoglycan entirely, relying instead on sterol-rich membranes, while others such as archaea use alternative polymers like pseudopeptidoglycan. These variations highlight the diversity of microbial strategies for maintaining cell envelope stability.
