Peptidoglycan is a complex, mesh-like polymer that forms a part of the bacterial cell wall. This unique structure surrounds the bacterial cytoplasmic membrane, providing structural rigidity and protection against the cell’s internal osmotic pressure. It acts as a protective exoskeleton, helping bacteria maintain their shape and withstand environmental challenges.
The Glycan Strands
The framework of peptidoglycan consists of long, linear polysaccharide chains, known as glycan strands. These strands are built from two alternating sugar derivatives: N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM). These sugar units are linked together in a repetitive pattern, forming the carbohydrate backbone of the peptidoglycan structure.
The connection between individual NAG and NAM units is formed by beta-1,4 glycosidic bonds. This robust linkage creates a durable sugar chain that serves as a structural element of the cell wall. The consistent arrangement of these disaccharide units ensures the stability and integrity of the peptidoglycan network.
The Peptide Side Chains
Attached to each N-acetylmuramic acid (NAM) residue within the glycan strand is a short chain of amino acids. These peptide side chains contain a feature: the inclusion of D-amino acids, such as D-alanine and D-glutamic acid.
Unlike L-amino acids, which are standard building blocks for proteins in most organisms, the presence of D-amino acids is characteristic of bacterial cell walls. This configuration contributes to the peptidoglycan’s resistance to degradation by proteases, which target L-amino acid linkages. The amino acid sequence of these peptide chains can vary between bacterial species, but a common arrangement includes L-alanine, D-glutamic acid, a diamino acid (like meso-diaminopimelic acid or L-lysine), and two D-alanines.
The Cross-linking Network
The glycan strands and their attached peptide side chains are interconnected to form a strong, three-dimensional network. This interconnection, known as cross-linking, provides the cell wall with its mechanical strength and rigidity. The process of forming these cross-links is carried out by enzymes called transpeptidases, which create covalent peptide bonds between adjacent peptide side chains.
The nature of this cross-linking differs between Gram-positive and Gram-negative bacteria. In Gram-negative bacteria, the peptide side chains form direct covalent bonds between the D-alanine at position 4 of one peptide and the meso-diaminopimelic acid (mDAP) at position 3 of an adjacent peptide side chain. This direct linkage contributes to a thinner peptidoglycan layer, 7-8 nanometers thick.
In contrast, Gram-positive bacteria utilize an interpeptide bridge to connect their glycan strands. This bridge, often composed of a short chain of amino acids (such as a pentaglycine bridge in Staphylococcus aureus), links the D-alanine of one peptide side chain to the L-lysine at position 3 of a neighboring peptide side chain. This bridging results in a thicker peptidoglycan layer in Gram-positive bacteria, ranging from 20 to 80 nanometers, which provides greater structural integrity and is a factor in their Gram stain classification.