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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
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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. |
format | Online Article Text |
id | pubmed-5343580 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
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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