The interactions of [14C]cefotetan with penicillin binding proteins of a wide variety of Gram-positive and gram-negative species

Abstract

Membrane preparations were made from a number of Gram-positive and Gram-negative bacterial strains. The ability of the membrane-bound penicillin-binding proteins (PBP) in these preparations to bind [14C]cefotetan has been studied. Increasing amounts of unlabelled benzylpenicillin were added and subsequently [14C]cefotetan was introduced to determine its ability to bind to additional proteins or to displace the pre-bound benzylpenicillin. In the Gram-positive series some quantitative binding differences between the two labelled compounds could be seen. However, in the majority of Gram-negative organisms tested cefotetan exhibited greatest affinity for PBP 3 and none for PBP 2. No new PBPs were detected using [14C]cefotetan, suggesting that the compound exerts its antibacterial effect by a mechanism similar to the other cephamycins. The high minimal inhibitory concentrations (MICs) of cefotetan found for the Gram-positive genera tested are reflected in only one organism by the failure to bind of some of its PBPs. In the majority of cases, permeability is assumed to play the dominant role in the relatively low sensitivity of these organisms to cefotetan.