DAPTOMYCIN, its membrane-active mechanism vs. that of other antimicrobial peptides

Biochimica Et Biophysica Acta. Biomembranes
Huey W Huang

Abstract

Over 3000 membrane-active antimicrobial peptides (AMPs) have been discovered, but only three of them have been approved by the U.S. Food and Drug Administration (FDA) for therapeutic applications, i.e., gramicidin, daptomycin and colistin. Of the three approved AMPs, daptomycin is a last-line-of-defense antibiotic for treating Gram-positive infections. However its use has already created bacterial resistance. To search for its substitutes that might counter the resistance, we need to understand its molecular mechanism. The mode of action of daptomycin appears to be causing bacterial membrane depolarization through ion leakage. Daptomycin forms a unique complex with calcium ions and phosphatidylglycerol molecules in membrane at a specific stoichiometric ratio: Dap2Ca3PG2. How does this complex promote ion conduction across the membrane? We hope that biophysics of peptide-membrane interaction can answer this question. This review summarizes the biophysical works that have been done on membrane-active AMPs to understand their mechanisms of action, including gramicidin, daptomycin, and underdeveloped pore-forming AMPs. The analysis suggests that daptomycin forms transient ionophores in the target membranes. We discuss questions tha...Continue Reading

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Citations

Jan 16, 2021·International Journal of Molecular Sciences·Francisco Ramos-Martín, Nicola D'Amelio
Feb 11, 2021·The Journal of Membrane Biology·Charles H ChenJakob P Ulmschneider
Feb 24, 2021·The Journal of Membrane Biology·Antje Pokorny, Paulo F Almeida
Jul 25, 2021·International Journal of Molecular Sciences·Benjamin LeytonMichel Abanto Marin
Sep 5, 2020·The Journal of Physical Chemistry. B·Andrea MescolaAndrea Alessandrini

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