title: Binding of monobactams to penicillin-binding proteins of Escherichia coli and Staphylococcus aureus: relation to antibacterial activity.
abstract: A series of novel monocyclic beta-lactam antibiotics having side chains related to penicillin, piperacillin, azlocillin, and cefotaxime were examined with respect to binding to essential penicillin-binding proteins (PBPs) in Escherichia coli and Staphylococcus aureus. In the penicillin series, there was poor binding to all essential PBPs of E. coli (greater than 100 micrograms/ml) but good binding to PBPs 1, 2, and 3 of S. aureus (approximately 1 microgram/ml). In the piperacillin and azlocillin series, there was good binding to PBP 3 of E. coli (0.1 microgram/ml) and PBPs 1, 2, and 3 of S. aureus (approximately 1 microgram/ml). In the cefotaxime series, there was generally good binding to PBP 3 of E. coli (0.1 micrograms/ml) but poor binding to PBPs 1, 2, and 3 of S. aureus (greater than or equal to 100 micrograms/ml). With a few exceptions in the cefotaxime series, antibacterial activity paralleled essential PBP binding. Binding studies with radioactively labeled compounds revealed no additional essential monobactam-binding proteins in the two organisms. The studies suggest that monobactams are intrinsically active against both gram-positive and gram-negative bacteria; the activity spectrum of a given monobactam is determined by the binding to essential PBPs, which in turn is determined by the nature of the substituents on the beta-lactam nucleus.
mesh_terms: D019881:Aminoacyltransferases; D000900:Anti-Bacterial Agents / Q000378:metabolism*; D001426:Bacterial Proteins; D002268:Carboxypeptidases / Q000037:antagonists & inhibitors; D002352:Carrier Proteins / Q000378:metabolism*; D004926:Escherichia coli / Q000187:drug effects / Q000378:metabolism*; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase; D046915:Penicillin-Binding Proteins; D010458:Peptidyl Transferases / Q000037:antagonists & inhibitors; D013211:Staphylococcus aureus / Q000187:drug effects / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002352:Carrier Proteins; D046915:Penicillin-Binding Proteins; D019881:Aminoacyltransferases; C022330:peptidoglycan transpeptidase; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002268:Carboxypeptidases; D002267:Muramoylpentapeptide Carboxypeptidase