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Title: Elucidating the bactericidal mechanism of action of the linear antimicrobial tetrapeptide BRBR-NH 2
Authors: Lau, Qiu Ying
Li, Jianguo
Sani, Marc-Antoine
Sinha, Sheetal
Li, Yan
Ng, Fui Mee
Kang, CongBao
Bhattacharjya, Surajit
Separovic, Frances
Verma, Chandra
Chia, Brian Cheng San
Keywords: Antimicrobial Peptide
Membrane Disruptor
DRNTU::Science::Biological sciences
Issue Date: 2018
Source: Lau, Q. Y., Li, J., Sani, M.-A., Sinha, S., Li, Y., Ng, F. M., . . . Chia, C. S. B. (2018). Elucidating the bactericidal mechanism of action of the linear antimicrobial tetrapeptide BRBR-NH 2. Biochimica et Biophysica Acta (BBA) - Biomembranes, 1860(8), 1517-1527. doi:10.1016/j.bbamem.2018.05.004
Series/Report no.: Biochimica et Biophysica Acta (BBA) - Biomembranes
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.
ISSN: 0005-2736
DOI: 10.1016/j.bbamem.2018.05.004
Rights: © 2018 Elsevier B.V. All rights reserved. This paper was published in Biochimica et Biophysica Acta (BBA) - Biomembranes and is made available with permission of Elsevier B.V.
Fulltext Permission: open
Fulltext Availability: With Fulltext
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