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Molecular Determinants for OMF Selectivity in Tripartite RND Multidrug Efflux Systems

dc.rights.licenseopenen_US
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorBOYER, Esther
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorDESSOLIN, Jean
dc.contributor.authorLUSTIG, Margaux
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorDECOSSAS, Marion
dc.contributor.authorPHAN, Gilles
dc.contributor.authorCECE, Quentin
dc.contributor.authorDURAND, Gregory
dc.contributor.authorDUBOIS, Veronique
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorSANSEN, Joris
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorTAVEAU, Jean-Christophe
dc.contributor.authorBROUTIN, Isabelle
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorDAURY, Laetitia
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorLAMBERT, Olivier
dc.date.accessioned2024-10-04T11:50:57Z
dc.date.available2024-10-04T11:50:57Z
dc.date.issued2022-01-18
dc.identifier.issn2079-6382en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/202259
dc.description.abstractEnTripartite multidrug RND efflux systems made of an inner membrane transporter, an outer membrane factor (OMF) and a periplasmic adaptor protein (PAP) form a canal to expel drugs across Gram-negative cell wall. Structures of MexA–MexB–OprM and AcrA–AcrB–TolC, from Pseudomonas aeruginosa and Escherichia coli, respectively, depict a reduced interfacial contact between OMF and PAP, making unclear the comprehension of how OMF is recruited. Here, we show that a Q93R mutation of MexA located in the α-hairpin domain increases antibiotic resistance in the MexAQ93R–MexB–OprM-expressed strain. Electron microscopy single-particle analysis reveals that this mutation promotes the formation of tripartite complexes with OprM and non-cognate components OprN and TolC. Evidence indicates that MexAQ93R self-assembles into a hexameric form, likely due to interprotomer interactions between paired R93 and D113 amino acids. C-terminal deletion of OprM prevents the formation of tripartite complexes when mixed with MexA and MexB components but not when replacing MexA with MexAQ93R. This study reveals the Q93R MexA mutation and the OprM C-terminal peptide as molecular determinants modulating the assembly process efficacy with cognate and non-cognate OMFs, even though they are outside the interfacial contact. It provides insights into how OMF selectivity operates during the formation of the tripartite complex.
dc.description.sponsorshipBiosenseurs originaux pour le criblage des ligands des Récepteurs Couplés aux Protéines G. Application au récepteur de la ghréline.en_US
dc.language.isoENen_US
dc.rightsAttribution-NonCommercial 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc/3.0/us/*
dc.subjectAntibiotic resistance
dc.subjectEfflux pump
dc.subjectRND
dc.title.enMolecular Determinants for OMF Selectivity in Tripartite RND Multidrug Efflux Systems
dc.typeArticle de revueen_US
dc.identifier.doi10.3390/antibiotics11020126en_US
dc.subject.halChimie/Matériauxen_US
dc.identifier.pubmed35203729en_US
bordeaux.journalAntibioticsen_US
bordeaux.page126en_US
bordeaux.volume11en_US
bordeaux.hal.laboratoriesCBMN : Chimie & de Biologie des Membranes & des Nano-objets - UMR 5248en_US
bordeaux.issue2en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionBordeaux INPen_US
bordeaux.institutionCNRSen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exportfalse
dc.rights.ccCC BY-NCen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Antibiotics&rft.date=2022-01-18&rft.volume=11&rft.issue=2&rft.spage=126&rft.epage=126&rft.eissn=2079-6382&rft.issn=2079-6382&rft.au=BOYER,%20Esther&DESSOLIN,%20Jean&LUSTIG,%20Margaux&DECOSSAS,%20Marion&PHAN,%20Gilles&rft.genre=article


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