Microbial Cell-Wall Polysaccharides - Peptidoglycans

Gram-positive bacteria contain a rigid peptidoglycan cell wall surrounding the cytoplasmic membrane. Gram-negative bacteria contain an additional third, outer layer. This wall is a complex structure with lipoproteins and lipopolysaccharides. Synthesis of two outer walls from different bacterial cells is described in this concept screen:

Staphylococcus aureus - The polysaccharide chain is an alternating polymer of N-acetylglucosamine and N-acetylmuramic acid. The carboxyl groups of all the N-acetylmuramic acid resides are linked to the terminal group of the tetrapeptide-L-alanyl-D--isoglutaminyl-L-lysyl-D-alanine. The biosynthesis can be considered to occur in the following three distinct stages:

> 1. Synthesis of UDP-N-acetylmuramyl pentapeptide - This reaction sequence begins with the synthesis of UDP-N-acetylmuramic acid from UDP-N-acetylglucosamine (see here). Figure 16.19 shows subsequent steps in which the pentapeptide is built onto the UDP-N-acetylmuramic acid carboxyl group. Note that these peptide bonds are made by specific ATP-dependent ligases, not ribosomes.

> 2. Polymerization of N-acetylglucosamine and N-acetylmuramylpentapeptide - This process involves the lipid carrier, undecaprenol phosphate, a 55-carbon compound containing 11 isoprenoid units, with phosphate linked at the terminus. To this phosphate, the N-acetylmuramylpentapeptide moiety from stage 1 is attached (Figure 16.20, step 1). Next, N-acetylglucosamine is added from UDP-N-acetylglucosamine (Figure 16.20, step 2), followed by the sequential addition of five glycyl residues, from glycyl transfer RNA (Figure 16.20, step 3). Next, the peptidodisaccharide unit is transported through the membrane (Figure 16.20, step 4). Last, the molecule is added to the reducing end of a preexisting peptidoglycan chain (Figure 16.20, step 5). The antibiotics bacitracin and vancomycin inhibit specific steps in this process, as shown in Figure 16.20.

> 3. Cross-linking of individual peptidoglycan strands - This transpeptidation reaction uses energy from cleavage of one peptide bond to form another. This process is shown in Figure 16.21. The cross-linking reaction is the target of action for the penicillins and the cephalosporins. Penicillin is thought to react irreversibly with the transpeptidase that catalyzes the cross-linking. Unfortunately, resistance to penicillin can be acquired by bacteria that synthesize lactamase, an enzyme that hydrolyzes the lactam ring of penicillin and destroys its ability to interfere with peptidoglycan synthesis.

Salmonella typhimurium - This organism's O antigen is the major lipopolysaccharide component of the outer membrane. Lipopolysaccharides contain repeating oligosaccharide units attached to a basal core polysaccharide. The latter is, in turn, attached to a complex called lipid A. The repeating oligosaccharide units provoke strong immune reactions. To avoid the immune response, bacteria change the O-antigen structure through extremely rapid genetic change. The mechanism for its synthesis is depicted in Figure 16.22.

See also: Biosynthesis of Glycoconjugates, N-Acetylglucosamine, N-Acetylmuramic Acid, Bacterial Cell Walls

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