Affiliation:
1. Department of Genetics, University of Leicester, Leicester, LE1 7RH, England
2. Ciba-Geigy Limited, CH-4002, Basel, Switzerland
Abstract
Thienamycin and clavulanic acid are new β-lactam derivatives with structures markedly different from those of penicillins or cephalosporins. Both derivatives had the same general mode of action as typical β-lactam antibiotics since they bound to precisely the same proteins as [
14
C]benzylpenicillin. Thienamycin showed high affinity for penicillin-binding proteins 1, 2, 4, 5, and 6 and a lower affinity for protein 3. Protein 2 had the highest affinity for thienamycin, and concentrations from the minimal morphological change concentration (0.1 μg/ml) up to about 0.6 μg/ml resulted in the conversion of
Escherichia coli
KN126 into large osmotically stable round cells. Above a concentration of 0.6 μg/ml, rapid cell lysis occurred with the release of the cell contents as spheroplasts. Clavulanic acid showed good affinity for penicillin-binding protein 2, moderate affinity for proteins 1, 4, 5, and 6, and low affinity for protein 3. Protein 2 had the highest affinity for clavulanic acid, and concentrations from the minimal morphological change concentration (30 μg/ml) up to about 50 μg/ml produced a mixture of slightly elongated, swollen, bulging, and lemon-shaped cells. Above a concentration of 50 μg/ml, rapid lysis occurred with production of spheroplasts. The properties of thienamycin and clavulanic acid were compared with those of the penicillins, cephalosporins, and amidinopenicillanic acids.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Cited by
112 articles.
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