The bacterial cell wall is a rigid layer external to the cytoplasmic membrane that maintains cell shape, withstands internal osmotic pressure, and provides protection against environmental stress. Its composition is the primary determinant of Gram staining classification.
Peptidoglycan Structure
Peptidoglycan (murein) is a polymer consisting of alternating N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM) residues linked by β-1,4 glycosidic bonds. Short peptide chains are attached to NAM residues — in E. coli, the peptide is L-Ala-D-Glu-meso-diaminopimelic acid (mDAP)-D-Ala. Adjacent peptide chains are cross-linked by transpeptidase enzymes, creating a strong, mesh-like sacculus that surrounds the cell.
Gram-Positive Cell Wall
The Gram-positive cell wall has a thick peptidoglycan layer (20–80 nm, approximately 20–40 layers) that retains crystal violet during Gram staining. Teichoic acids, polymers of glycerol or ribitol phosphate, are covalently attached to peptidoglycan and extend outward, binding Mg²⁺ ions and regulating autolysin activity. Lipoteichoic acids are teichoic acids anchored to the cytoplasmic membrane via a glycolipid, contributing to the negative surface charge. Surface proteins include adhesins, enzymes, and M protein in Streptococcus pyogenes.
Gram-Negative Cell Wall
The Gram-negative cell wall has a thin peptidoglycan layer (2–7 nm, 1–3 layers) located in the periplasmic space between the inner and outer membranes. The outer membrane is an asymmetric lipid bilayer with phospholipids in the inner leaflet and lipopolysaccharides (LPS) in the outer leaflet. LPS consists of lipid A (endotoxin), core polysaccharide, and O-antigen — lipid A is responsible for the toxicity of Gram-negative sepsis. Porins are transmembrane proteins (e.g., OmpF, OmpC) that form channels for passive diffusion of small hydrophilic molecules. Braun’s lipoprotein connects the outer membrane to the peptidoglycan layer, maintaining structural integrity.
Mycobacterial Cell Wall
The mycobacterial cell wall is exceptionally thick and waxy due to mycolic acids (long-chain α-alkyl, β-hydroxy fatty acids) covalently linked to arabinogalactan-peptidoglycan. This complex provides resistance to acids and alcohols (acid-fast staining), desiccation, many antibiotics, and host immune mechanisms. The cell wall accounts for up to 60% of the dry weight of Mycobacterium species.
Cell Wall Functions
The cell wall maintains cell shape (coccus, bacillus, spirillum) through the rigid peptidoglycan sacculus and prevents osmotic lysis by withstanding internal pressures of 5–20 atmospheres. It provides protection against toxic molecules, lysozyme, and bacteriophages, and serves as an anchor for surface structures including flagella, pili, and secretion systems.
Clinical Relevance
Beta-lactam antibiotics (penicillins, cephalosporins) inhibit peptidoglycan cross-linking by binding transpeptidase enzymes (PBPs). Lysozyme, found in tears and saliva, cleaves the β-1,4 glycosidic bond in peptidoglycan, causing osmotic lysis. LPS (endotoxin) from Gram-negative bacteria triggers strong inflammatory responses and septic shock.
