Penicillins peptidoglycan crosslinking

Fig. 8.3 A, comparison of the stmcture of the nucleus of the penicillin molecule with B, the D-alanyl-D-alanine end group of the precursor of bacterial peptidoglycan. The broken lines show the correspondence in position between the labile bond of penicillin and the bond broken during the transpeptidation reaction associated with the crosslinking in peptidoglycan. 

Penicillin kills only growing bacteria by preventing proper crosslinking of the peptidoglycan... 

Inhibition of transpeptidase Some PBPs catalyze formation of the cross-linkages between peptidoglycan chains. Penicillins inhibit this transpeptidase-catalyzed reaction, thus hindering the formation of crosslinks essential for cell wall integrity. As a result of this blockade of cell wall synthesis, the Park peptide , UDP-acetylmuramyl-L-Ala-D-GIn-L-Lys-D-Ala-D-Ala, accumulates. 

Beta-lactam penicillins prevent the biosynthesis of a dipeptidoglycan which forms the peptidoglycan cell wall in bacteria. This results in cell death and bactericidal activity. Specifically, they acylate a specific bacterial D-transpeptidase, which inactivates this enzyme and it therefore cannot form peptide crosslinks of two linear peptidoglycan strands for cell wall formation. 

Mode of action. Penicillins act by inhibiting the enzymes (Penicillin Binding Proteins, PBPs) involved in the crosslinking of the peptidoglycan layer of the cell wall which protects the bacterium from its environment incapable of withstanding... 

A peptidoglycan complex, possessing a linear, non-crosslinked structure composed of disaccharide-pentapeptide units, has been isolated from a penicillin-treated mutant of Brevibacterium divaricatum requiring biotin for growth.The peptidoglycan fragments appear to be synthesized after incubation of the cells with penicillin. 

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