Biochemical and genetical approaches to the mechanism of action of penicillin.
Since the discovery in 1965 that penicillin inhibits the transpeptidation reaction in peptidoglycan synthesis, a considerable effort has been put into the purification of enzymes that catalyse this reaction. This has resulted in the recognition that bacteria possess multiple forms of these penicillin-sensitive enzymes and has made it difficult to identify the precise target that penicillin inactivates to kill the organism. Recently penicillin-sensitive enzymes have been detected and studies as penicillin-binding proteins on sodium dodecyl sulphate polyacrylamide gels. The availability of this convenient method for identifying penicillin-sensitive enzymes has allowed biochemical and genetical approaches to be used to dissect their roles in the lethal effects of penicillin and other beta-lactam antibiotics. Three penicillin-binding proteins (1 B, 2 and 3) have been identified as killing targets for penicillin in Escherichia coli, whereas four other binding proteins are not implicated in the mechanism of action of the antibiotic. The complex biological effects that beta-lactam antibiotics produce on the growth of E. coli can be explained by their interaction with the three killing targets. Progress in the correlation of penicillin-binding proteins with penicillin-sensitive enzymes and in the development of strains of E. coli that overproduce penicillin-binding proteins is discussed.
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000378:metabolism; D002352:Carrier Proteins / Q000096:biosynthesis / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase; D046915:Penicillin-Binding Proteins; D010405:Penicillinase / Q000378:metabolism; D010406:Penicillins / Q000096:biosynthesis / Q000378:metabolism / Q000494:pharmacology*; D010458:Peptidyl Transferases; D047090:beta-Lactams / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002352:Carrier Proteins; D046915:Penicillin-Binding Proteins; D010406:Penicillins; D047090:beta-Lactams; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase; D010405:Penicillinase