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Interaction of Antimicrobial Lipopeptides with Bacterial Lipid Bilayers.

Authors
  • Shahane, Ganesh1
  • Ding, Wei2
  • Palaiokostas, Michail2
  • Azevedo, Helena S2
  • Orsi, Mario3
  • 1 Institute of Bioengineering, Queen Mary University of London, Mile End Road, London, E1 4NS, UK.
  • 2 School of Engineering & Materials Science, Queen Mary University of London, Mile End Road, London, E1 4NS, UK.
  • 3 Department of Applied Sciences, University of the West of England, Coldharbour Lane, Bristol, BS16 1QY, UK. [email protected]
Type
Published Article
Journal
The Journal of Membrane Biology
Publisher
Springer-Verlag
Publication Date
Oct 01, 2019
Volume
252
Issue
4-5
Pages
317–329
Identifiers
DOI: 10.1007/s00232-019-00068-3
PMID: 31098677
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

The resistance of pathogens to traditional antibiotics is currently a global issue of enormous concern. As the discovery and development of new antibiotics become increasingly challenging, synthetic antimicrobial lipopeptides (AMLPs) are now receiving renewed attention as a new class of antimicrobial agents. In contrast to traditional antibiotics, AMLPs act by physically disrupting the cell membrane (rather than targeting specific proteins), thus reducing the risk of inducing bacterial resistance. In this study, we use microsecond-timescale atomistic molecular dynamics simulations to quantify the interaction of a short AMLP (C16-KKK) with model bacterial lipid bilayers. In particular, we investigate how fundamental transmembrane properties change in relation to a range of lipopeptide concentrations. A number of structural, mechanical, and dynamical features are found to be significantly altered in a non-linear fashion. At 10 mol% concentration, lipopeptides have a condensing effect on bacterial bilayers, characterized by a decrease in the area per lipid and an increase in the bilayer order. Higher AMLP concentrations of 25 and 40 mol% destabilize the membrane by disrupting the bilayer core structure, inducing membrane thinning and water leakage. Important transmembrane properties such as the lateral pressure and dipole potential profiles are also affected. Potential implications on membrane function and associated proteins are discussed.

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