Peptidoglycan, bacterial cell walls penicillin action

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... 

Because peptidoglycans are unique to bacterial cell walls, with no known homologous structures in mammals, the enzymes responsible for their synthesis are ideal targets for antibiotic action. Antibiotics that hit specific bacterial targets are sometimes called magic bullets. Penicillin and its many synthetic analogs have been used to treat bacterial infections since these drugs came into wide application in World War II. 

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. 

Beta-lactam antibiotics act on enzymes called penicillin-binding proteins (PBP) near the bacterial cell wall. When beta-lactam antibiotics bind covalently and irreversibly to the PBP, they interfere with the production of cell-wall peptidoglycans, causing cell lysis in hypoosmotic environments. Differences in the spectrum of activity and actions of beta-lactam antibiotics result from their relative affinity for different PBP. 

Selective inhibition of bacterial cell wall synthesis (penicillins, cephalosporins, bacitracin, vancomycin). Following attachment to receptors (penicillinbinding proteins), p-lactam antibiotics inhibit transpeptidation enzymes and thereby block the final stage of peptidoglycan sysnthesis. This action is followed by inactivation of an inhibitor of autolytic enzymes in the bacterial cell wall. Bacitracin and vancomycin inhibit early stages of peptidoglycan synthesis. 

Peptidoglycans are components of bacterial cell walls and consist of heteropolysaccharide chains cross-linked by short peptide chains. These cell walls bear the antigenic determinants when exposed to them, humans (and other mammalian species) develop specific antibodies to defend against bacteria. Bacterial virulence is also related to substances associated with the cell wall. Cell wall synthesis is the target for the action of the penicillins and cephalosporins. 

Mechanism of action of penicillin. The conformation of the D-alanyl-D-alanine portion of the peptidoglycan of bacterial cell walls is similar to that of the lactam ring of penicillin, so that the enzyme cleaves the lactam ring (at the site marked ( ) to form a stable penicilloyl-enzyme complex. 

Peptidoglycans.—The biosynthesis of the peptidoglycans of bacterial cell walls and the action of penicillin on the biosynthesis of peptidoglycans have been re-viewed. Other reviews have discussed the effects of endogenous and exogenous factors on the primary structures of bacterial peptidoglycans and the com-... 

The main site of action of penicillin is a membrane-bound transpeptidase in the bacterial cytoplasmic membrane. It performs two tasks initially, it attracts the D-alanyl-D-alanine end of the monomer which is waiting to be polymerized to form new cell-wall. This monomer is a peptidoglycan, that is to say it consists of muropeptide units (Section 5.3) bound together through the condensation of their carbohydrate components. D-Alanine is the recognition signal for this enzyme. The next step is an acylation of the enzyme by the peptidoglycan, with loss of one molecule of D-Alanine ... 

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