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

Elucidating the bactericidal mechanism of action of the linear antimicrobial tetrapeptide BRBR-NH2 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Biochimica et Biophysica Acta Biomembranes Or Bba Biomembranes Elsevier

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Publisher
Elsevier
Copyright
Copyright © 2018 Elsevier B.V.
ISSN
0005-2736
eISSN
1879-2642
D.O.I.
10.1016/j.bbamem.2018.05.004
Publisher site
See Article on Publisher Site

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.

Journal

Biochimica et Biophysica Acta Biomembranes Or Bba BiomembranesElsevier

Published: Aug 1, 2018

References

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