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Development of novel broad-spectrum antimicrobial lipopeptides derived from plantaricin NC8 β

Bacterial resistance towards antibiotics is a major global health issue. Very few novel antimicrobial agents and therapies have been made available for clinical use during the past decades, despite an increasing need. Antimicrobial peptides have been intensely studied, many of which have shown great...

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Autores principales: Wiman, Emanuel, Zattarin, Elisa, Aili, Daniel, Bengtsson, Torbjörn, Selegård, Robert, Khalaf, Hazem
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10011573/
https://www.ncbi.nlm.nih.gov/pubmed/36914718
http://dx.doi.org/10.1038/s41598-023-31185-8
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author Wiman, Emanuel
Zattarin, Elisa
Aili, Daniel
Bengtsson, Torbjörn
Selegård, Robert
Khalaf, Hazem
author_facet Wiman, Emanuel
Zattarin, Elisa
Aili, Daniel
Bengtsson, Torbjörn
Selegård, Robert
Khalaf, Hazem
author_sort Wiman, Emanuel
collection PubMed
description Bacterial resistance towards antibiotics is a major global health issue. Very few novel antimicrobial agents and therapies have been made available for clinical use during the past decades, despite an increasing need. Antimicrobial peptides have been intensely studied, many of which have shown great promise in vitro. We have previously demonstrated that the bacteriocin Plantaricin NC8 αβ (PLNC8 αβ) from Lactobacillus plantarum effectively inhibits Staphylococcus spp., and shows little to no cytotoxicity towards human keratinocytes. However, due to its limitations in inhibiting gram-negative species, the aim of the present study was to identify novel antimicrobial peptidomimetic compounds with an enhanced spectrum of activity, derived from the β peptide of PLNC8 αβ. We have rationally designed and synthesized a small library of lipopeptides with significantly improved antimicrobial activity towards both gram-positive and gram-negative bacteria, including the ESKAPE pathogens. The lipopeptides consist of 16 amino acids with a terminal fatty acid chain and assemble into micelles that effectively inhibit and kill bacteria by permeabilizing their cell membranes. They demonstrate low hemolytic activity and liposome model systems further confirm selectivity for bacterial lipid membranes. The combination of lipopeptides with different antibiotics enhanced the effects in a synergistic or additive manner. Our data suggest that the novel lipopeptides are promising as future antimicrobial agents, however additional experiments using relevant animal models are necessary to further validate their in vivo efficacy.
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spelling pubmed-100115732023-03-15 Development of novel broad-spectrum antimicrobial lipopeptides derived from plantaricin NC8 β Wiman, Emanuel Zattarin, Elisa Aili, Daniel Bengtsson, Torbjörn Selegård, Robert Khalaf, Hazem Sci Rep Article Bacterial resistance towards antibiotics is a major global health issue. Very few novel antimicrobial agents and therapies have been made available for clinical use during the past decades, despite an increasing need. Antimicrobial peptides have been intensely studied, many of which have shown great promise in vitro. We have previously demonstrated that the bacteriocin Plantaricin NC8 αβ (PLNC8 αβ) from Lactobacillus plantarum effectively inhibits Staphylococcus spp., and shows little to no cytotoxicity towards human keratinocytes. However, due to its limitations in inhibiting gram-negative species, the aim of the present study was to identify novel antimicrobial peptidomimetic compounds with an enhanced spectrum of activity, derived from the β peptide of PLNC8 αβ. We have rationally designed and synthesized a small library of lipopeptides with significantly improved antimicrobial activity towards both gram-positive and gram-negative bacteria, including the ESKAPE pathogens. The lipopeptides consist of 16 amino acids with a terminal fatty acid chain and assemble into micelles that effectively inhibit and kill bacteria by permeabilizing their cell membranes. They demonstrate low hemolytic activity and liposome model systems further confirm selectivity for bacterial lipid membranes. The combination of lipopeptides with different antibiotics enhanced the effects in a synergistic or additive manner. Our data suggest that the novel lipopeptides are promising as future antimicrobial agents, however additional experiments using relevant animal models are necessary to further validate their in vivo efficacy. Nature Publishing Group UK 2023-03-13 /pmc/articles/PMC10011573/ /pubmed/36914718 http://dx.doi.org/10.1038/s41598-023-31185-8 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Wiman, Emanuel
Zattarin, Elisa
Aili, Daniel
Bengtsson, Torbjörn
Selegård, Robert
Khalaf, Hazem
Development of novel broad-spectrum antimicrobial lipopeptides derived from plantaricin NC8 β
title Development of novel broad-spectrum antimicrobial lipopeptides derived from plantaricin NC8 β
title_full Development of novel broad-spectrum antimicrobial lipopeptides derived from plantaricin NC8 β
title_fullStr Development of novel broad-spectrum antimicrobial lipopeptides derived from plantaricin NC8 β
title_full_unstemmed Development of novel broad-spectrum antimicrobial lipopeptides derived from plantaricin NC8 β
title_short Development of novel broad-spectrum antimicrobial lipopeptides derived from plantaricin NC8 β
title_sort development of novel broad-spectrum antimicrobial lipopeptides derived from plantaricin nc8 β
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10011573/
https://www.ncbi.nlm.nih.gov/pubmed/36914718
http://dx.doi.org/10.1038/s41598-023-31185-8
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