Imperial College London
Alternate

DrBrianRobertson

Faculty of Medicine, Department of Infectious Disease

Reader in Systems Microbiology
 
 
 
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b.robertson

 
 
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Location

 

3.41Flowers buildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Khara:2017:10.1016/j.actbio.2017.04.032,
author = {Khara, JS and Obuobi, S and Wang, Y and Hamilton, MS and Robertson, BD and Newton, SM and Yang, YY and Langford, PR and Ee, PLR},
doi = {10.1016/j.actbio.2017.04.032},
journal = {Acta Biomaterialia},
pages = {103--114},
title = {Disruption of drug-resistant biofilms using de novo designed short α-helicalantimicrobial peptides with idealized facial amphiphilicity},
url = {http://dx.doi.org/10.1016/j.actbio.2017.04.032},
volume = {57},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The escalating threat of antimicrobial resistance has increased pressure to develop novel therapeutic strategies to tackle drug-resistant infections. Antimicrobial peptides have emerged as a promising class of therapeutics for various systemic and topical clinical applications. In this study, the de novo design of α-helical peptides with idealized facial amphiphilicities, based on an understanding of the pertinent features of protein secondary structures, is presented. Synthetic amphiphiles composed of the backbone sequence (X1Y1Y2X2)n, where X1 and X2 are hydrophobic residues (Leu or Ile or Trp), Y1 and Y2 are cationic residues (Lys), and n is the number repeat units (2 or 2.5 or 3), demonstrated potent broad-spectrum antimicrobial activities against clinical isolates of drug-susceptible and multi-drug resistant bacteria. Live-cell imaging revealed that the most selective peptide, (LKKL)3, promoted rapid permeabilization of bacterial membranes. Importantly, (LKKL)3 not only suppressed biofilm growth, but effectively disrupted mature biofilms after only 2 h of treatment. The peptides (LKKL)3 and (WKKW)3 suppressed the production of LPS-induced pro-inflammatory mediators to levels of unstimulated controls at low micromolar concentrations. Thus, the rational design strategies proposed herein can be implemented to develop potent, selective and multifunctional α-helical peptides to eradicate drug-resistant biofilm-associated infections.
AU  - Khara,JS
AU  - Obuobi,S
AU  - Wang,Y
AU  - Hamilton,MS
AU  - Robertson,BD
AU  - Newton,SM
AU  - Yang,YY
AU  - Langford,PR
AU  - Ee,PLR
DO  - 10.1016/j.actbio.2017.04.032
EP  - 114
PY  - 2017///
SN  - 1878-7568
SP  - 103
TI  - Disruption of drug-resistant biofilms using de novo designed short α-helicalantimicrobial peptides with idealized facial amphiphilicity
T2  - Acta Biomaterialia
UR  - http://dx.doi.org/10.1016/j.actbio.2017.04.032
UR  - http://hdl.handle.net/10044/1/48232
VL  - 57
ER  -
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