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Neutron diffraction studies of the interaction between amphotericin B and lipid-sterol model membranes

Over the last 50 years or so, amphotericin has been widely employed in treating life-threatening systemic fungal infections. Its usefulness in the clinic, however, has always been circumscribed by its dose-limiting side-effects, and it is also now compromised by an increasing incidence of pathogen r...

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Autores principales: Foglia, Fabrizia, Lawrence, M. Jayne, Demė, Bruno, Fragneto, Giovanna, Barlow, David
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3482691/
https://www.ncbi.nlm.nih.gov/pubmed/23110248
http://dx.doi.org/10.1038/srep00778
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author Foglia, Fabrizia
Lawrence, M. Jayne
Demė, Bruno
Fragneto, Giovanna
Barlow, David
author_facet Foglia, Fabrizia
Lawrence, M. Jayne
Demė, Bruno
Fragneto, Giovanna
Barlow, David
author_sort Foglia, Fabrizia
collection PubMed
description Over the last 50 years or so, amphotericin has been widely employed in treating life-threatening systemic fungal infections. Its usefulness in the clinic, however, has always been circumscribed by its dose-limiting side-effects, and it is also now compromised by an increasing incidence of pathogen resistance. Combating these problems through development of new anti-fungal agents requires detailed knowledge of the drug's molecular mechanism, but unfortunately this is far from clear. Neutron diffraction studies of the drug's incorporation within lipid-sterol membranes have here been performed to shed light on this problem. The drug is shown to disturb the structures of both fungal and mammalian membranes, and co-localises with the membrane sterols in a manner consistent with trans-membrane pore formation. The differences seen in the membrane lipid ordering and in the distributions of the drug-ergosterol and drug-cholesterol complexes within the membranes are consistent with the drug's selectivity for fungal vs. human cells.
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spelling pubmed-34826912012-10-29 Neutron diffraction studies of the interaction between amphotericin B and lipid-sterol model membranes Foglia, Fabrizia Lawrence, M. Jayne Demė, Bruno Fragneto, Giovanna Barlow, David Sci Rep Article Over the last 50 years or so, amphotericin has been widely employed in treating life-threatening systemic fungal infections. Its usefulness in the clinic, however, has always been circumscribed by its dose-limiting side-effects, and it is also now compromised by an increasing incidence of pathogen resistance. Combating these problems through development of new anti-fungal agents requires detailed knowledge of the drug's molecular mechanism, but unfortunately this is far from clear. Neutron diffraction studies of the drug's incorporation within lipid-sterol membranes have here been performed to shed light on this problem. The drug is shown to disturb the structures of both fungal and mammalian membranes, and co-localises with the membrane sterols in a manner consistent with trans-membrane pore formation. The differences seen in the membrane lipid ordering and in the distributions of the drug-ergosterol and drug-cholesterol complexes within the membranes are consistent with the drug's selectivity for fungal vs. human cells. Nature Publishing Group 2012-10-29 /pmc/articles/PMC3482691/ /pubmed/23110248 http://dx.doi.org/10.1038/srep00778 Text en Copyright © 2012, Macmillan Publishers Limited. All rights reserved http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
spellingShingle Article
Foglia, Fabrizia
Lawrence, M. Jayne
Demė, Bruno
Fragneto, Giovanna
Barlow, David
Neutron diffraction studies of the interaction between amphotericin B and lipid-sterol model membranes
title Neutron diffraction studies of the interaction between amphotericin B and lipid-sterol model membranes
title_full Neutron diffraction studies of the interaction between amphotericin B and lipid-sterol model membranes
title_fullStr Neutron diffraction studies of the interaction between amphotericin B and lipid-sterol model membranes
title_full_unstemmed Neutron diffraction studies of the interaction between amphotericin B and lipid-sterol model membranes
title_short Neutron diffraction studies of the interaction between amphotericin B and lipid-sterol model membranes
title_sort neutron diffraction studies of the interaction between amphotericin b and lipid-sterol model membranes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3482691/
https://www.ncbi.nlm.nih.gov/pubmed/23110248
http://dx.doi.org/10.1038/srep00778
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