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Interactions of Linear Analogues of Battacin with Negatively Charged Lipid Membranes
The increasing resistance of bacteria to available antibiotics has stimulated the search for new antimicrobial compounds with less specific mechanisms of action. These include the ability to disrupt the structure of the cell membrane, which in turn leads to its damage. In this context, amphiphilic l...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001853/ https://www.ncbi.nlm.nih.gov/pubmed/33801980 http://dx.doi.org/10.3390/membranes11030192 |
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author | Burdach, Kinga Tymecka, Dagmara Urban, Aneta Lasek, Robert Bartosik, Dariusz Sek, Slawomir |
author_facet | Burdach, Kinga Tymecka, Dagmara Urban, Aneta Lasek, Robert Bartosik, Dariusz Sek, Slawomir |
author_sort | Burdach, Kinga |
collection | PubMed |
description | The increasing resistance of bacteria to available antibiotics has stimulated the search for new antimicrobial compounds with less specific mechanisms of action. These include the ability to disrupt the structure of the cell membrane, which in turn leads to its damage. In this context, amphiphilic lipopeptides belong to the class of the compounds which may fulfill this requirement. In this paper, we describe two linear analogues of battacin with modified acyl chains to tune the balance between the hydrophilic and hydrophobic portion of lipopeptides. We demonstrate that both compounds display antimicrobial activity with the lowest values of minimum inhibitory concentrations found for Gram-positive pathogens. Therefore, their mechanism of action was evaluated on a molecular level using model lipid films mimicking the membrane of Gram-positive bacteria. The surface pressure measurements revealed that both lipopeptides show ability to bind and incorporate into the lipid monolayers, resulting in decreased ordering of lipids and membrane fluidization. Atomic force microscopy (AFM) imaging demonstrated that the exposure of the model bilayers to lipopeptides leads to a transition from the ordered gel phase to disordered liquid crystalline phase. This observation was confirmed by attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FTIR) results, which revealed that lipopeptide action causes a substantial increase in the average tilt angle of lipid acyl chains with respect to the surface normal to compensate for lipopeptide insertion into the membrane. Moreover, the peptide moieties in both molecules do not adopt any well-defined secondary structure upon binding with the lipid membrane. It was also observed that a small difference in the structure of a lipophilic chain, altering the balance between hydrophobic and hydrophilic portion of the molecules, results in different insertion depth of the active compounds. |
format | Online Article Text |
id | pubmed-8001853 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-80018532021-03-28 Interactions of Linear Analogues of Battacin with Negatively Charged Lipid Membranes Burdach, Kinga Tymecka, Dagmara Urban, Aneta Lasek, Robert Bartosik, Dariusz Sek, Slawomir Membranes (Basel) Article The increasing resistance of bacteria to available antibiotics has stimulated the search for new antimicrobial compounds with less specific mechanisms of action. These include the ability to disrupt the structure of the cell membrane, which in turn leads to its damage. In this context, amphiphilic lipopeptides belong to the class of the compounds which may fulfill this requirement. In this paper, we describe two linear analogues of battacin with modified acyl chains to tune the balance between the hydrophilic and hydrophobic portion of lipopeptides. We demonstrate that both compounds display antimicrobial activity with the lowest values of minimum inhibitory concentrations found for Gram-positive pathogens. Therefore, their mechanism of action was evaluated on a molecular level using model lipid films mimicking the membrane of Gram-positive bacteria. The surface pressure measurements revealed that both lipopeptides show ability to bind and incorporate into the lipid monolayers, resulting in decreased ordering of lipids and membrane fluidization. Atomic force microscopy (AFM) imaging demonstrated that the exposure of the model bilayers to lipopeptides leads to a transition from the ordered gel phase to disordered liquid crystalline phase. This observation was confirmed by attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FTIR) results, which revealed that lipopeptide action causes a substantial increase in the average tilt angle of lipid acyl chains with respect to the surface normal to compensate for lipopeptide insertion into the membrane. Moreover, the peptide moieties in both molecules do not adopt any well-defined secondary structure upon binding with the lipid membrane. It was also observed that a small difference in the structure of a lipophilic chain, altering the balance between hydrophobic and hydrophilic portion of the molecules, results in different insertion depth of the active compounds. MDPI 2021-03-10 /pmc/articles/PMC8001853/ /pubmed/33801980 http://dx.doi.org/10.3390/membranes11030192 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ). |
spellingShingle | Article Burdach, Kinga Tymecka, Dagmara Urban, Aneta Lasek, Robert Bartosik, Dariusz Sek, Slawomir Interactions of Linear Analogues of Battacin with Negatively Charged Lipid Membranes |
title | Interactions of Linear Analogues of Battacin with Negatively Charged Lipid Membranes |
title_full | Interactions of Linear Analogues of Battacin with Negatively Charged Lipid Membranes |
title_fullStr | Interactions of Linear Analogues of Battacin with Negatively Charged Lipid Membranes |
title_full_unstemmed | Interactions of Linear Analogues of Battacin with Negatively Charged Lipid Membranes |
title_short | Interactions of Linear Analogues of Battacin with Negatively Charged Lipid Membranes |
title_sort | interactions of linear analogues of battacin with negatively charged lipid membranes |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001853/ https://www.ncbi.nlm.nih.gov/pubmed/33801980 http://dx.doi.org/10.3390/membranes11030192 |
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