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dc.rights.licenseopenen_US
dc.contributor.authorNITENBERG, Milene
dc.contributor.authorBENAROUCHE, Anais
dc.contributor.authorMANITI, Ofelia
dc.contributor.authorMARION, Estelle
dc.contributor.authorMARSOLLIER, Laurent
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorGEAN, Julie
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorDUFOURC, Erick J.
dc.contributor.authorCAVALLER, Jean-Francois
dc.contributor.authorCANAAN, Stephane
dc.contributor.authorGIRARD-EGROT, Agnes P.
dc.date.accessioned2020-04-09T09:44:19Z
dc.date.available2020-04-09T09:44:19Z
dc.date.issued2018
dc.identifier.issn1553-7366en_US
dc.identifier.otherhttps://figshare.com/articles/The_potent_effect_of_mycolactone_on_lipid_membranes/5776560en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/4197
dc.description.abstractEnMycolactone 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 mu M, 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.
dc.language.isoENen_US
dc.subject.enCell membranes
dc.subject.enLipids
dc.subject.enCholesterol
dc.subject.enToxins
dc.subject.enMembrane proteins
dc.subject.enIntegral membrane proteins
dc.subject.enIsotherms
dc.subject.enDetergents
dc.title.enThe potent effect of mycolactone on lipid membranes
dc.title.alternativePLoS Pathogen_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1371/journal.ppat.1006814
dc.subject.halChimie/Matériauxen_US
bordeaux.journalPlos Pathogensen_US
bordeaux.volume14en_US
bordeaux.hal.laboratoriesInstitut de Chimie & de Biologie des Membranes & des Nano-objets (CBMN) - UMR 5248
bordeaux.issue1en_US
bordeaux.institutionBordeaux INPen_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.identifier.funderIDAssociation Instituts Carnoten_US
hal.identifierhal-03184354
hal.version1
hal.date.transferred2021-03-29T11:57:16Z
hal.exporttrue
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