Elucidating the bactericidal mechanism of action of the linear antimicrobial tetrapeptide BRBR-NH2

Biochimica Et Biophysica Acta. Biomembranes
Qiu Ying LauCheng San Brian Chia

Abstract

Linear antimicrobial peptides, with their rapid bactericidal mode of action, are well-suited for development as topical antibacterial drugs. We recently designed a synthetic linear 4-residue peptide, BRBR-NH2, with potent bactericidal activity against Staphylococcus aureus (MIC 6.25 μM), the main causative pathogen of human skin infections with an unknown mechanism of action. Herein, we describe a series of experiments conducted to gain further insights into its mechanism of action involving electron microscopy, artificial membrane dye leakage, solution- and solid-state NMR spectroscopy followed by molecular dynamics simulations. Experimental results point towards a SMART (Soft Membranes Adapt and Respond, also Transiently) mechanism of action, suggesting that the peptide can be developed as a topical antibacterial agent for treating drug-resistant Staphylococcus aureus infections.

Citations

Feb 26, 2019·Future Medicinal Chemistry·Catarina Dias, Amélia P Rauter
Jan 1, 2019·Australian Journal of Chemistry·William C Wimley, Kalina Hristova
Dec 19, 2020·International Journal of Molecular Sciences·Stanislav R KurpeOxana V Galzitskaya

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