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Mechanism of action of EM 49, membrane-active peptide antibiotic
Abstract:
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.
Insights
Octapeptin (EM 49) acts like an uncoupler, disrupting bacterial membrane potential and affecting bacterial respiration. This peptide antibiotic increases proton permeability and lowers ATP levels, impacting bacterial survival.
Area of Science:
- Microbiology
- Biochemistry
- Molecular Biology
Background:
- Octapeptin (EM 49) is a known membrane-active peptide antibiotic.
- Previous research indicated EM 49 affects bacterial membrane structure.
Purpose of the Study:
- To investigate the metabolic effects of octapeptin (EM 49) on bacterial cells.
- To compare the mechanism of action of octapeptin with polymyxin B.
Main Methods:
- Bacterial respiration assays at various peptide concentrations.
- Measurement of membrane proton permeability.
- Quantification of intracellular adenosine 5'-triphosphate (ATP) pool size.
Main Results:
- Octapeptin (EM 49) stimulated bacterial respiration at sub-lethal concentrations and inhibited it at lethal concentrations.
- The peptide increased membrane proton permeability and decreased ATP pool size.
- Polymyxin B showed different effects on bacterial respiration compared to octapeptin.
Conclusions:
- Octapeptin's primary action is to disrupt cytoplasmic membrane ion permeability, leading to membrane potential dissipation.
- These effects are similar to uncouplers of oxidative phosphorylation.
- Octapeptin exhibits distinct metabolic impacts compared to polymyxin B.