Mechanism of action of EM 49, membrane-active peptide antibiotic

EM 49 (recently renamed octapeptin) is a membrane-active peptide antibiotic that has been reported to affect the structure of bacterial membranes. (K. S. Rosenthal, P. E. Swanson, and D. R. Storm, Biochemistry 15:5783-5792, 1976). In this study, it is shown that the effects of EM 49 on bacterial metabolism are similar to those of uncouplers of oxidative phosphorylation. EM 49 stimulated bacterial respiration within a narrow concentration range corresponding to minimum inhibitory concentrations and inhibited respiration at concentrations comparable to minimum biocidal concentrations. In addition, the peptide increased membrane proton permeability and lowered the adenosine 5'-triphosphate pool size. Parallel studies done with the related antibiotic polymyxin B demonstrated that the two peptides differed considerably in their effects on bacterial respiration. In contrast to EM 49, polymyxin B did not stimulate respiration at any concentration. It is proposed that the primary action of EM 49 is to disrupt the selective ion permeability of the cytoplasmic membrane, thereby relaxing the membrane potential.