Elucidating the bactericidal mechanism of action of the linear antimicrobial tetrapeptide BRBR-NH 2

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 ca...

Full description

Bibliographic Details
Main 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
Other Authors: Interdisciplinary Graduate School (IGS)
Format: Journal Article
Language:English
Published: 2019
Subjects:
Online Access:https://hdl.handle.net/10356/90094
http://hdl.handle.net/10220/48405
_version_ 1826110925120208896
author 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
author2 Interdisciplinary Graduate School (IGS)
author_facet Interdisciplinary Graduate School (IGS)
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
author_sort Lau, Qiu Ying
collection NTU
description 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.
first_indexed 2024-10-01T02:42:09Z
format Journal Article
id ntu-10356/90094
institution Nanyang Technological University
language English
last_indexed 2024-10-01T02:42:09Z
publishDate 2019
record_format dspace
spelling ntu-10356/900942023-02-28T17:03:03Z Elucidating the bactericidal mechanism of action of the linear antimicrobial tetrapeptide BRBR-NH 2 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 Interdisciplinary Graduate School (IGS) School of Biological Sciences Advanced Environmental Biotechnology Centre Nanyang Environment and Water Research Institute Antimicrobial Peptide Membrane Disruptor DRNTU::Science::Biological sciences 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. ASTAR (Agency for Sci., Tech. and Research, S’pore) MOE (Min. of Education, S’pore) Accepted version 2019-05-28T04:16:00Z 2019-12-06T17:40:32Z 2019-05-28T04:16:00Z 2019-12-06T17:40:32Z 2018 Journal Article 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 0005-2736 https://hdl.handle.net/10356/90094 http://hdl.handle.net/10220/48405 10.1016/j.bbamem.2018.05.004 en Biochimica et Biophysica Acta (BBA) - Biomembranes © 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. 41 p. application/pdf
spellingShingle Antimicrobial Peptide
Membrane Disruptor
DRNTU::Science::Biological sciences
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
Elucidating the bactericidal mechanism of action of the linear antimicrobial tetrapeptide BRBR-NH 2
title Elucidating the bactericidal mechanism of action of the linear antimicrobial tetrapeptide BRBR-NH 2
title_full Elucidating the bactericidal mechanism of action of the linear antimicrobial tetrapeptide BRBR-NH 2
title_fullStr Elucidating the bactericidal mechanism of action of the linear antimicrobial tetrapeptide BRBR-NH 2
title_full_unstemmed Elucidating the bactericidal mechanism of action of the linear antimicrobial tetrapeptide BRBR-NH 2
title_short Elucidating the bactericidal mechanism of action of the linear antimicrobial tetrapeptide BRBR-NH 2
title_sort elucidating the bactericidal mechanism of action of the linear antimicrobial tetrapeptide brbr nh 2
topic Antimicrobial Peptide
Membrane Disruptor
DRNTU::Science::Biological sciences
url https://hdl.handle.net/10356/90094
http://hdl.handle.net/10220/48405
work_keys_str_mv AT lauqiuying elucidatingthebactericidalmechanismofactionofthelinearantimicrobialtetrapeptidebrbrnh2
AT lijianguo elucidatingthebactericidalmechanismofactionofthelinearantimicrobialtetrapeptidebrbrnh2
AT sanimarcantoine elucidatingthebactericidalmechanismofactionofthelinearantimicrobialtetrapeptidebrbrnh2
AT sinhasheetal elucidatingthebactericidalmechanismofactionofthelinearantimicrobialtetrapeptidebrbrnh2
AT liyan elucidatingthebactericidalmechanismofactionofthelinearantimicrobialtetrapeptidebrbrnh2
AT ngfuimee elucidatingthebactericidalmechanismofactionofthelinearantimicrobialtetrapeptidebrbrnh2
AT kangcongbao elucidatingthebactericidalmechanismofactionofthelinearantimicrobialtetrapeptidebrbrnh2
AT bhattacharjyasurajit elucidatingthebactericidalmechanismofactionofthelinearantimicrobialtetrapeptidebrbrnh2
AT separovicfrances elucidatingthebactericidalmechanismofactionofthelinearantimicrobialtetrapeptidebrbrnh2
AT vermachandra elucidatingthebactericidalmechanismofactionofthelinearantimicrobialtetrapeptidebrbrnh2
AT chiabrianchengsan elucidatingthebactericidalmechanismofactionofthelinearantimicrobialtetrapeptidebrbrnh2