Modulation of bacteriolysis by cooperative effects of penicillin-binding proteins 1a and 3 in Escherichia coli.
Escherichia coli characteristically lyses upon treatment with most beta-lactam antimicrobial agents. In contrast, an investigational aminothiazole cephem, CGP 31523A, produced a new combination of antibacterial effects: it was highly bactericidal without causing cell wall degradation or lysis. Killing was associated with the formation of vacuolated filaments. Because the compound bound to penicillin-binding proteins (PBPs) 1a and 3, we investigated the role of PBP 3 in modulation of lysis caused by inhibition of PBP 1a. A temperature-sensitive mutant with a nonfunctional PBP 3 lysed when treated with CGP 31523A. The combination of a PBP 1 inhibitor (cefsulodin) and a PBP 3 inhibitor (aztreonam) also caused filamentation and death without lysis of wild-type cells over a narrow concentration range. We conclude that cooperative effects between PBPs in E. coli can lead to a dissociation of bacterial killing and lysis.
D000217:Acyltransferases / Q000502:physiology*; D001398:Aztreonam / Q000494:pharmacology; D001426:Bacterial Proteins; D001433:Bacteriolysis / Q000187:drug effects*; D002352:Carrier Proteins; D002441:Cefsulodin / Q000494:pharmacology; D002511:Cephalosporins / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects*; D006602:Hexosyltransferases / Q000037:antagonists & inhibitors / Q000502:physiology*; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors / Q000502:physiology*; D002267:Muramoylpentapeptide Carboxypeptidase; D009154:Mutation; D046915:Penicillin-Binding Proteins; D010458:Peptidyl Transferases / Q000037:antagonists & inhibitors / Q000502:physiology*
D001426:Bacterial Proteins; D002352:Carrier Proteins; D002511:Cephalosporins; D009097:Multienzyme Complexes; D046915:Penicillin-Binding Proteins; C044430:CGP 31523A; D000217:Acyltransferases; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase; D001398:Aztreonam; D002441:Cefsulodin