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Antimicrobial peptide cWFW kills by combining lipid phase separation with autolysis

The synthetic cyclic hexapeptide cWFW (cyclo(RRRWFW)) has a rapid bactericidal activity against both Gram-positive and Gram-negative bacteria. Its detailed mode of action has, however, remained elusive. In contrast to most antimicrobial peptides, cWFW neither permeabilizes the membrane nor transloca...

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Autores principales: Scheinpflug, Kathi, Wenzel, Michaela, Krylova, Oxana, Bandow, Julia E., Dathe, Margitta, Strahl, Henrik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5343580/
https://www.ncbi.nlm.nih.gov/pubmed/28276520
http://dx.doi.org/10.1038/srep44332
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author Scheinpflug, Kathi
Wenzel, Michaela
Krylova, Oxana
Bandow, Julia E.
Dathe, Margitta
Strahl, Henrik
author_facet Scheinpflug, Kathi
Wenzel, Michaela
Krylova, Oxana
Bandow, Julia E.
Dathe, Margitta
Strahl, Henrik
author_sort Scheinpflug, Kathi
collection PubMed
description The synthetic cyclic hexapeptide cWFW (cyclo(RRRWFW)) has a rapid bactericidal activity against both Gram-positive and Gram-negative bacteria. Its detailed mode of action has, however, remained elusive. In contrast to most antimicrobial peptides, cWFW neither permeabilizes the membrane nor translocates to the cytoplasm. Using a combination of proteome analysis, fluorescence microscopy, and membrane analysis we show that cWFW instead triggers a rapid reduction of membrane fluidity both in live Bacillus subtilis cells and in model membranes. This immediate activity is accompanied by formation of distinct membrane domains which differ in local membrane fluidity, and which severely disrupts membrane protein organisation by segregating peripheral and integral proteins into domains of different rigidity. These major membrane disturbances cause specific inhibition of cell wall synthesis, and trigger autolysis. This novel antibacterial mode of action holds a low risk to induce bacterial resistance, and provides valuable information for the design of new synthetic antimicrobial peptides.
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spelling pubmed-53435802017-03-14 Antimicrobial peptide cWFW kills by combining lipid phase separation with autolysis Scheinpflug, Kathi Wenzel, Michaela Krylova, Oxana Bandow, Julia E. Dathe, Margitta Strahl, Henrik Sci Rep Article The synthetic cyclic hexapeptide cWFW (cyclo(RRRWFW)) has a rapid bactericidal activity against both Gram-positive and Gram-negative bacteria. Its detailed mode of action has, however, remained elusive. In contrast to most antimicrobial peptides, cWFW neither permeabilizes the membrane nor translocates to the cytoplasm. Using a combination of proteome analysis, fluorescence microscopy, and membrane analysis we show that cWFW instead triggers a rapid reduction of membrane fluidity both in live Bacillus subtilis cells and in model membranes. This immediate activity is accompanied by formation of distinct membrane domains which differ in local membrane fluidity, and which severely disrupts membrane protein organisation by segregating peripheral and integral proteins into domains of different rigidity. These major membrane disturbances cause specific inhibition of cell wall synthesis, and trigger autolysis. This novel antibacterial mode of action holds a low risk to induce bacterial resistance, and provides valuable information for the design of new synthetic antimicrobial peptides. Nature Publishing Group 2017-03-09 /pmc/articles/PMC5343580/ /pubmed/28276520 http://dx.doi.org/10.1038/srep44332 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Scheinpflug, Kathi
Wenzel, Michaela
Krylova, Oxana
Bandow, Julia E.
Dathe, Margitta
Strahl, Henrik
Antimicrobial peptide cWFW kills by combining lipid phase separation with autolysis
title Antimicrobial peptide cWFW kills by combining lipid phase separation with autolysis
title_full Antimicrobial peptide cWFW kills by combining lipid phase separation with autolysis
title_fullStr Antimicrobial peptide cWFW kills by combining lipid phase separation with autolysis
title_full_unstemmed Antimicrobial peptide cWFW kills by combining lipid phase separation with autolysis
title_short Antimicrobial peptide cWFW kills by combining lipid phase separation with autolysis
title_sort antimicrobial peptide cwfw kills by combining lipid phase separation with autolysis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5343580/
https://www.ncbi.nlm.nih.gov/pubmed/28276520
http://dx.doi.org/10.1038/srep44332
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