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Dual Action of BPC194: A Membrane Active Peptide Killing Bacterial Cells

Membrane active peptides can perturb the lipid bilayer in several ways, such as poration and fusion of the target cell membrane, and thereby efficiently kill bacterial cells. We probe here the mechanistic basis of membrane poration and fusion caused by membrane-active, antimicrobial peptides. We show that the cyclic antimicrobial peptide, BPC194, inhibits growth of Gram-negative bacteria and ruptures the outer and inner membrane at the onset of killing, suggesting that not just poration is taking place at the cell envelope. To simplify the system and to better understand the mechanism of action, we performed Förster resonance energy transfer and cryogenic transmission electron microscopy studies in model membranes and show that the BPC194 causes fusion of vesicles. The fusogenic action is accompanied by leakage as probed by dual-color fluorescence burst analysis at a single liposome level. Atomistic molecular dynamics simulations reveal how the peptides are able to simultaneously perturb the membrane towards porated and fused states. We show that the cyclic antimicrobial peptides trigger both fusion and pore formation and that such large membrane perturbations have a similar mechanistic basis

PLoS ONE, 2013, vol. 8, núm. 4, p. e61541

Public Library of Science

Author: Moiset, Gemma
Díaz i Cirac, Anna
Stuart, Marc C. A.
Marrink, Siewert J.
Sengupta, Durba
Poolman, Bert
Date: 2013 April
Abstract: Membrane active peptides can perturb the lipid bilayer in several ways, such as poration and fusion of the target cell membrane, and thereby efficiently kill bacterial cells. We probe here the mechanistic basis of membrane poration and fusion caused by membrane-active, antimicrobial peptides. We show that the cyclic antimicrobial peptide, BPC194, inhibits growth of Gram-negative bacteria and ruptures the outer and inner membrane at the onset of killing, suggesting that not just poration is taking place at the cell envelope. To simplify the system and to better understand the mechanism of action, we performed Förster resonance energy transfer and cryogenic transmission electron microscopy studies in model membranes and show that the BPC194 causes fusion of vesicles. The fusogenic action is accompanied by leakage as probed by dual-color fluorescence burst analysis at a single liposome level. Atomistic molecular dynamics simulations reveal how the peptides are able to simultaneously perturb the membrane towards porated and fused states. We show that the cyclic antimicrobial peptides trigger both fusion and pore formation and that such large membrane perturbations have a similar mechanistic basis
Format: application/pdf
ISSN: 1932-6203
Document access: http://hdl.handle.net/10256/7760
Language: eng
Publisher: Public Library of Science
Collection: Reproducció digital del document publicat a: http://dx.doi.org/10.1371/journal.pone.0061541
Articles publicats (D-Q)
Is part of: PLoS ONE, 2013, vol. 8, núm. 4, p. e61541
Rights: Attribution 3.0 Spain
Rights URI: http://creativecommons.org/licenses/by/3.0/es/
Subject: Antibiòtics pèptids
Peptide antibiotics
Membranes (Biologia)
Membranes (Biology)
Bioquímica
Biochemistry
Title: Dual Action of BPC194: A Membrane Active Peptide Killing Bacterial Cells
Type: info:eu-repo/semantics/article
Repository: DUGiDocs

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