title: Binding of thienamycin and clavulanic acid to the penicillin-binding proteins of Escherichia coli K-12.
abstract: Thienamycin and clavulanic acid are new beta-lactam derivatives with structures markedly different from those of penicillins or cephalosporins. Both derivatives had the same general mode of action as typical beta-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 mug/ml) up to about 0.6 mug/ml resulted in the conversion of Escherichia coli KN126 into large osmotically stable round cells. Above a concentration of 0.6 mug/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 mug/ml) up to about 50 mug/ml produced a mixture of slightly elongated, swollen, bulging, and lemon-shaped cells. Above a concentration of 50 mug/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.
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism* / Q000494:pharmacology; D001426:Bacterial Proteins / Q000378:metabolism*; D001667:Binding, Competitive; D055598:Chemical Phenomena; D002621:Chemistry; D004926:Escherichia coli / Q000187:drug effects / Q000378:metabolism*; D007769:Lactams / Q000378:metabolism / Q000494:pharmacology; D010400:Penicillin G / Q000378:metabolism; D011485:Protein Binding; D013845:Thienamycins
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D007769:Lactams; D013845:Thienamycins; D010400:Penicillin G; C015537:thienamycin