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.