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The potent effect of mycolactone on lipid membranes

Mycolactone is a lipid-like endotoxin synthesized by an environmental human pathogen, Mycobacterium ulcerans, the causal agent of Buruli ulcer disease. Mycolactone has pleiotropic effects on fundamental cellular processes (cell adhesion, cell death and inflammation). Various cellular targets of myco...

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Autores principales: Nitenberg, Milène, Bénarouche, Anaïs, Maniti, Ofelia, Marion, Estelle, Marsollier, Laurent, Géan, Julie, Dufourc, Erick J., Cavalier, Jean-François, Canaan, Stéphane, Girard-Egrot, Agnès P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5779694/
https://www.ncbi.nlm.nih.gov/pubmed/29320578
http://dx.doi.org/10.1371/journal.ppat.1006814
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author Nitenberg, Milène
Bénarouche, Anaïs
Maniti, Ofelia
Marion, Estelle
Marsollier, Laurent
Géan, Julie
Dufourc, Erick J.
Cavalier, Jean-François
Canaan, Stéphane
Girard-Egrot, Agnès P.
author_facet Nitenberg, Milène
Bénarouche, Anaïs
Maniti, Ofelia
Marion, Estelle
Marsollier, Laurent
Géan, Julie
Dufourc, Erick J.
Cavalier, Jean-François
Canaan, Stéphane
Girard-Egrot, Agnès P.
author_sort Nitenberg, Milène
collection PubMed
description Mycolactone is a lipid-like endotoxin synthesized by an environmental human pathogen, Mycobacterium ulcerans, the causal agent of Buruli ulcer disease. Mycolactone has pleiotropic effects on fundamental cellular processes (cell adhesion, cell death and inflammation). Various cellular targets of mycolactone have been identified and a literature survey revealed that most of these targets are membrane receptors residing in ordered plasma membrane nanodomains, within which their functionalities can be modulated. We investigated the capacity of mycolactone to interact with membranes, to evaluate its effects on membrane lipid organization following its diffusion across the cell membrane. We used Langmuir monolayers as a cell membrane model. Experiments were carried out with a lipid composition chosen to be as similar as possible to that of the plasma membrane. Mycolactone, which has surfactant properties, with an apparent saturation concentration of 1 μM, interacted with the membrane at very low concentrations (60 nM). The interaction of mycolactone with the membrane was mediated by the presence of cholesterol and, like detergents, mycolactone reshaped the membrane. In its monomeric form, this toxin modifies lipid segregation in the monolayer, strongly affecting the formation of ordered microdomains. These findings suggest that mycolactone disturbs lipid organization in the biological membranes it crosses, with potential effects on cell functions and signaling pathways. Microdomain remodeling may therefore underlie molecular events, accounting for the ability of mycolactone to attack multiple targets and providing new insight into a single unifying mechanism underlying the pleiotropic effects of this molecule. This membrane remodeling may act in synergy with the other known effects of mycolactone on its intracellular targets, potentiating these effects.
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spelling pubmed-57796942018-02-08 The potent effect of mycolactone on lipid membranes Nitenberg, Milène Bénarouche, Anaïs Maniti, Ofelia Marion, Estelle Marsollier, Laurent Géan, Julie Dufourc, Erick J. Cavalier, Jean-François Canaan, Stéphane Girard-Egrot, Agnès P. PLoS Pathog Research Article Mycolactone is a lipid-like endotoxin synthesized by an environmental human pathogen, Mycobacterium ulcerans, the causal agent of Buruli ulcer disease. Mycolactone has pleiotropic effects on fundamental cellular processes (cell adhesion, cell death and inflammation). Various cellular targets of mycolactone have been identified and a literature survey revealed that most of these targets are membrane receptors residing in ordered plasma membrane nanodomains, within which their functionalities can be modulated. We investigated the capacity of mycolactone to interact with membranes, to evaluate its effects on membrane lipid organization following its diffusion across the cell membrane. We used Langmuir monolayers as a cell membrane model. Experiments were carried out with a lipid composition chosen to be as similar as possible to that of the plasma membrane. Mycolactone, which has surfactant properties, with an apparent saturation concentration of 1 μM, interacted with the membrane at very low concentrations (60 nM). The interaction of mycolactone with the membrane was mediated by the presence of cholesterol and, like detergents, mycolactone reshaped the membrane. In its monomeric form, this toxin modifies lipid segregation in the monolayer, strongly affecting the formation of ordered microdomains. These findings suggest that mycolactone disturbs lipid organization in the biological membranes it crosses, with potential effects on cell functions and signaling pathways. Microdomain remodeling may therefore underlie molecular events, accounting for the ability of mycolactone to attack multiple targets and providing new insight into a single unifying mechanism underlying the pleiotropic effects of this molecule. This membrane remodeling may act in synergy with the other known effects of mycolactone on its intracellular targets, potentiating these effects. Public Library of Science 2018-01-10 /pmc/articles/PMC5779694/ /pubmed/29320578 http://dx.doi.org/10.1371/journal.ppat.1006814 Text en © 2018 Nitenberg et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Nitenberg, Milène
Bénarouche, Anaïs
Maniti, Ofelia
Marion, Estelle
Marsollier, Laurent
Géan, Julie
Dufourc, Erick J.
Cavalier, Jean-François
Canaan, Stéphane
Girard-Egrot, Agnès P.
The potent effect of mycolactone on lipid membranes
title The potent effect of mycolactone on lipid membranes
title_full The potent effect of mycolactone on lipid membranes
title_fullStr The potent effect of mycolactone on lipid membranes
title_full_unstemmed The potent effect of mycolactone on lipid membranes
title_short The potent effect of mycolactone on lipid membranes
title_sort potent effect of mycolactone on lipid membranes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5779694/
https://www.ncbi.nlm.nih.gov/pubmed/29320578
http://dx.doi.org/10.1371/journal.ppat.1006814
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