title: Affinity of cefonicid, a long-acting cephalosporin, for the penicillin-binding proteins of Escherichia coli K-12.
abstract: The binding of cefonicid (SK&F 75073), a new parenteral cephalosporin, to the penicillin-binding proteins (PBPs) of Escherichia coli K-12 (strain KN-126) was determined by competitive binding studies versus benzyl[14C]penicillin. Cefonicid showed its greatest affinity for PBPs 1a greater than 3 greater than 1b, bound with low affinity to PBPs 4 greater than 2, and did not bind to PBPs 5 and 6. Provisional affinity constants (cefonicid concentration that gave 50% inhibition of [14C]penicillin binding) were determined: PBP 1a, less than 0.25 microgram/ml; PBP 3, 0.7 microgram/ml; PBP 1b, 10 micrograms/ml; PBP 4, 26 micrograms/ml; PBP 2, 90 micrograms/ml; PBPs 5 and 6 greater than 256 micrograms/ml. Direct binding studies with [14C]-cefonicid confirmed this pattern of binding. Subinhibitory concentrations of cefonicid (MIC, broth 0.2 microgram/ml, agar 0.4 microgram/ml) induced filamentation of E. coli KN-126. This implies that PBP 3 is the primary inhibitory site despite the higher affinity of PBP 1a for this cephalosporin.
mesh_terms: D001426:Bacterial Proteins; D002250:Carbon Radioisotopes; D002268:Carboxypeptidases / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002435:Cefamandole / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D015790:Cefonicid; D004926:Escherichia coli / Q000378:metabolism*; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase / Q000378:metabolism*; D046915:Penicillin-Binding Proteins; D010406:Penicillins / Q000378:metabolism; D010458:Peptidyl Transferases
chemical_list: D001426:Bacterial Proteins; D002250:Carbon Radioisotopes; D002352:Carrier Proteins; D046915:Penicillin-Binding Proteins; D010406:Penicillins; D002435:Cefamandole; D015790:Cefonicid; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002268:Carboxypeptidases; D002267:Muramoylpentapeptide Carboxypeptidase