Most procaryotes have a rigid cell wall. The cell wall is an essential structure that protects the cell protoplast from mechanical damage and from osmotic rupture or lysis. Procaryotes usually live in relatively dilute environments such that the accumulation of solutes inside the procaryotic cell cytoplasm greatly exceeds the total solute concentration in the outside environment. Thus, the osmotic pressure against the inside of the plasma membrane may be the equivalent of 10-25 atm. Since the membrane is a delicate, plastic structure, it must be restrained by an outside wall made of porous, rigid material that has high tensile strength. Such a material is murein, the ubiquitous component of bacterial cell walls.

Murein is a unique type of peptidoglycan, a polymer of disaccharides (glycan) cross-linked by short chains of amino acids (peptide). Many types of peptidoglycan exist. All Bacterial peptidoglycans contain N-acetylmuramic acid, which is the definitive component of murein. The cell walls of Archaea may be composed of protein, polysaccharides, or peptidoglycan-like molecules, but never do they contain murein. This feature distinguishes the Bacteria from the Archaea.

In the Gram-positive Bacteria (those that retain the purple crystal violet dye when subjected to the Gram-staining procedure), the cell wall consists of several layers of peptidoglycan. Running perpendicular to the peptidoglycan sheets is a group of molecules called teichoic acids which are unique to the Gram-positive cell wall (Figure 14).
 
Figure 14.  Structure of the Gram-positive bacterial cell wall. The wall is relatively thick and consists of many layers of peptidoglycan interspersed with teichoic acids that run perpendicular to the peptidoglycan sheets.

In the Gram-negative Bacteria (which do not retain the crystal violet), the cell wall is composed of a single layer of peptidoglycan surrounded by a membranous structure called the outer membrane. The outer membrane of Gram-negative bacteria invariably contains a unique component, lipopolysaccharide (LPS or endotoxin), which is toxic to animals. In Gram-negative bacteria the outer membrane is usually thought of as part of the cell wall (Figure 15).

Figure 16. The structure of the muramic acid subunit of the peptidoglycan of Escherichia coli. This is the type of murein found in most Gram-negative bacteria. The glycan backbone is a repeat polymer of two amino sugars, N-acetylglucosamine (G) and N-acetylmuramic acid (M). Attached to the N-acetylmuramic acid is a tetrapeptide consisting of L-ala-D-glu-DAP-D-ala. b. Abbreviated structure of the muramic acid subunit. c. Nearby tetrapeptide side chains may be linked to one another by an interpeptide bond between DAP on one chain and D-ala on the other. d. The polymeric form of the molecule.

Strands of murein are assembled in the periplasm from about 10 muramic acid subunits. Then the strands are connected to form a continuous glycan molecule that encompasses the cell. Wherever their proximity allows it, the tetrapeptide chains that project from the glycan backbone can be cross-linked by an interpeptide bond between a free amino group on DAP and a free carboxy group on a nearby D-ala. The assembly of peptidoglycan on the outside of the plasma membrane is mediated by a group of periplasmic enzymes, which are transglycosylases, transpeptidases and carboxypeptidases. The mechanism of action of penicillin and related beta-lactam antibiotics is to block transpeptidase and carboxypeptidase enzymes during their assembly of the murein cell wall. Hence, the beta lactam antibiotics are said to "block cell wall synthesis" in the bacteria.

The glycan backbone of the peptidoglycan molecule can be cleaved by an enzyme called lysozyme that is present in animal serum, tissues and secretions, and in the phagocytic lysosome. The function of lysozyme is to lyse bacterial cells as a constitutive defense against bacterial pathogens. Some Gram-positive bacteria are very sensitive to lysozyme and the enzyme is quite active at low concentrations. Lachrymal secretions (tears) can be diluted 1:40,000 and retain the ability to lyse certain bacterial cells. Gram-negative bacteria are less vulnerable to attack by lysozyme because their peptidoglycan is shielded by the outer membrane. The exact site of lysozymal cleavage is the beta 1,4 bond between N-acetylmuramic acid (M) and N-acetylglucosamine (G) , such that the muramic acid subunit shown in Figure 16(a) is the result of the action of lysozyme on bacterial peptidoglycan.

In Gram-positive bacteria there are numerous different peptide arrangements among peptidoglycans. The best studied is the murein of Staphylococcus aureus shown in Figure 17 below. In place of DAP (in E. coli) is the diamino acid, L-lysine (L-lys), and in place of the interpeptide bond (in Gram-negatives) is an interpeptide bridge of amino acids that connects a free amino group on lysine to a free carboxy group on D-ala of a nearby tetrapeptide side chain. This arrangement apparently allows for more frequent cross-bonding between nearby tetrapeptide side chains. In S. aureus, the interpeptide bridge is a peptide consisting of 5 glycine molecules (called a pentaglycine bridge). Assembly of the interpeptide bridge in Gram-positive murein is inhibited by the beta lactam antibiotics in the same manner as the interpeptide bond in Gram-negative murein. Gram-positive bacteria are more sensitive to penicillin than Gram-negative bacteria because the peptidoglycan is not protected by an outer membrane and it is a more abundant molecule. In Gram-positive bacteria, peptidoglycans may vary in the amino acid in place of DAP or L-lys in position 3 of the tetrapeptide, and in the exact composition of the interpeptide bridge. At least eight different types of peptidoglycan exist in Gram-positive bacteria.

Figure 17. Schematic diagram of the peptidoglycan sheet of Staphylococcus aureus. G = N-acetyl-glucosamine; M = N-acetyl-muramic acid; L-ala = L-alanine; D-ala = D-alanine; D-glu = D-glutamic acid; L-lys = L-lysine. This is one type of murein found in Gram-positive bacteria. Compared to the E. coli peptidoglycan (Figure 7) there is L-lys in place of DAP (diaminopimelic acid) in the tetrapeptide. The free amino group of L-lys is substituted with a glycine pentapeptide (gly-gly-gly-gly-gly-) which then becomes an interpeptide bridge forming a link with a carboxy group from D-ala in an adjacent tetrapeptide side chain. Gram-positive peptidoglycans differ from species to species, mainly in regards to the amino acids in the third position of the tetrapeptide side chain and in the amino acid composition of the interpeptide bridge.

Gram-negative bacteria may contain a single monomolecular layer of murein in their cell walls while Gram-positive bacteria are thought to have several layers or "wraps" of peptidoglycan. Closely associated with the layers of peptidoglycan in Gram-positive bacteria are a group of molecules called teichoic acids. Teichoic acids are linear polymers of polyglycerol or polyribitol substituted with phosphates and a few amino acids and sugars. The teichoic acid polymers are occasionally anchored to the plasma membrane (called lipoteichoic acid, LTA) apparently directed outward at right angles to the layers of peptidoglycan. The functions of teichoic acid are not known. They are essential to viability of Gram-positive bacteria in the wild. One idea is that they provide a channel of regularly-oriented negative charges for threading positively charged substances through the complicated peptidoglycan network. Another theory is that teichoic acids are in some way involved in the regulation and assembly of muramic acid subunits on the outside of the plasma membrane. There are instances, particularly in the streptococci, wherein teichoic acids have been implicated in the adherence of the bacteria to tissue surfaces.