Peptidoglycans in bacterial cell-walls

Lysozyme (egg) 1 129 13 900 Enzyme capable of degrading peptidoglycan in bacterial cell walls... 

A variety of enzymatic mechanisms for antibiotic resistance are known. Hydrolysis of the lactam rings of /3-lactams, cephalosporins, and carbapenams destroys their ability to inhibit transpeptidases that cross-link peptidoglycan in bacterial cell walls. Modification of aminoglycoside antibiotics by acetylation, phosphorylation, or adenylation interferes with their ability to bind to the 16S subunit of the ribosome. Streptogramin activity can be destroyed by acetylation or by an elimination reaction that opens the lactone ring. The enzymes responsible for these detoxification reactions evolved in response to naturally occurring antibiotics, but are easily adapted to modify semisynthetic and completely synthetic antibiotics. For example, only a few point mutations are needed to enhance the ability of TEM /3-lactamases to hydrolyze third-generation cephalosporins such as cefotaxime and ceftazidime. ... 

Lysozyme is a good example of an enzyme that catalyzes chemical reactions in the cell. Lysozyme acts to kill bacteria by cleaving the covalent bond between the alternating polysaccharides that compose peptidoglycan in bacterial cell walls. The human salivary defense proteins and lysozyme are known to exert a wide antimicrobial activity against a number of bacterial, viral, and fungal pathogens in vitro. Therefore, these proteins, alone or in combinations, have been incorporated as preservatives in foods and pharmaceuticals as well as in oral health care products to restore saliva s own antimicrobial capacity in patients with dry mouth. These antimicrobials used in oral health... 

The chemistry and biochemistry of the linkage units between teichoic acid and peptidoglycan in bacterial cell walls have been reviewed. Changes in the cell walls of mutants of Bacillus subtilis induced by temperature have been reflected in the production of different proportions of teichoic acid to peptidoglycan. ... 

Coley, J., Tarelli, E., Archibald, A.R. and Baddiley, J. The Linkage Between Teichoic Acid and Peptidoglycan in Bacterial Cell Walls , FEBS Letters (1918), 88, 1-9... 

Mode of action Interferes with bacterial cell wall synthesis during active multiplication, causing cell wall death and resultant bactericidal activity Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins, which in turn inhibit the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls bacteria usually lyse from ongoing autolytic enzyme activity... 

This enzyme catalyzes the transamination of a wide spectrum of a-amino acids and a-keto (or 2-oxo) acids, demonstrating absolute specificity for their D-isomers. The most likely physiologic role is to provide D-amino acids for peptidoglycan synthesis in bacterial cell wall formation. 

Another enzyme-activated inhibitor is the streptomyces antibiotic D-cycloserine (oxamycin), an antitubercular drug that resembles D-alanine in structure. A potent inhibitor of alanine racemase, it also inhibits die non-PLP, ATP-dependent, D-alanyl-D-alanine synthetase which is needed in the biosynthesis of die peptidoglycan of bacterial cell walls. 

Penicillins and cephalosporins have similar mechanisms of action. They both interfere with the terminal step in bacterial cell wall formation by preventing proper cross-linking of the peptidoglycan. 

J. van Heijenoort, Biosynthesis of Bacterial Peptidoglycan Unit. In Bacterial Cell Wall] J. M. Ghuysen, R. Hakenbeck, Eds. Elsevier Medical Press Amsterdam, 1994 pp 39-54. 

Phosphomycin, introduced in 1972, inhibits enolpyruvial transferase, an enzyme catalyzing an early step in bacterial cell wall biosynthesis. Inhibition results in reduced synthesis of peptidoglycan, an important component in the bacterial cell wall. Phosphomycin is bactericidal against Escherichia coii and Enterobacter faecaiis infections. 

Higashi Y, Strominger JL, Sweeley CC. Biosynthesis of the peptidoglycan of bacterial cell walls. XXI. Isolation of free Css-isoprenoid alcohol and of lipid intermediates in peptidoglycan synthesis from Staphylococcus aureus. J Biol Chem 1970 245-3697. 

Lysozyme 3.4 14.3 Enzyme, hydrolysing peptidoglycan links in bacterial cell wall... 

The antibacterial activity of BLAs is due to the inhibition of transpeptidase enzymes which are involved in bacterial cell wall biosynthesis. The transpeptidases or PBPs catalyze peptidoglycan cross-linking. 

Pacidamycins, napsamycins, mureidomycins, and sansanmycins are uridyl peptide antibiotics isolated from Streptomyces sp. strains and show potent inhibitory activity against phosphoMurVAc-pentapeptide translocase (MraY), an essential enzyme in bacterial cell wall peptidoglycan biosynthesis [269, 270]. 

As mentioned, lysozyme hydrolyzes glycosidic linkages in the peptidoglycan polymer of gram-positive bacterial cell walls. The structure of an oligosaccharide similar to the polysaccharide found in bacterial cell walls is shown in Fig. 24.16. //-Acetylglucosamine (NAG) and //-acetylmuramic acid (NAM) form alternating repeat units in this polysaccharide. 

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