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Molecular Determinants for OMF Selectivity in Tripartite RND Multidrug Efflux Systems

dc.rights.licenseopenen_US
dc.contributor.authorBOYER, Esther
dc.contributor.authorDESSOLIN, Jean
dc.contributor.authorLUSTIG, Margaux
dc.contributor.authorDECOSSAS, Marion
dc.contributor.authorPHAN, Gilles
dc.contributor.authorCECE, Quentin
dc.contributor.authorDURAND, Grégory
hal.structure.identifierMicrobiologie Fondamentale et Pathogénicité [MFP]
dc.contributor.authorDUBOIS, Véronique
dc.contributor.authorSANSEN, Joris
dc.contributor.authorTAVEAU, Jean-Christophe
dc.contributor.authorBROUTIN, Isabelle
dc.contributor.authorDAURY, Laetitia
dc.contributor.authorLAMBERT, Olivier
dc.date.accessioned2023-05-17T07:34:33Z
dc.date.available2023-05-17T07:34:33Z
dc.date.issued2022
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/182176
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.language.isoENen_US
dc.rightsAttribution 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/*
dc.subject.enantibiotic resistance
dc.subject.enefflux pump
dc.subject.enRND
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.halSciences du Vivant [q-bio]/Biochimie, Biologie Moléculaire/Biologie structurale [q-bio.BM]en_US
dc.subject.halSciences du Vivant [q-bio]/Microbiologie et Parasitologie/Bactériologieen_US
dc.subject.halSciences du Vivant [q-bio]/Sciences pharmaceutiques/Pharmacologieen_US
bordeaux.journalAntibioticsen_US
bordeaux.page126en_US
bordeaux.volume11en_US
bordeaux.hal.laboratoriesMFP (Laboratoire Microbiologie Fondamentale et Pathogénicité) - UMR 5234en_US
bordeaux.issue2en_US
bordeaux.institutionCNRSen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.import.sourcehal
hal.identifierhal-03815594
hal.version1
hal.exportfalse
workflow.import.sourcehal
dc.rights.ccPas de Licence CCen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Antibiotics&rft.date=2022&rft.volume=11&rft.issue=2&rft.spage=126&rft.epage=126&rft.au=BOYER,%20Esther&DESSOLIN,%20Jean&LUSTIG,%20Margaux&DECOSSAS,%20Marion&PHAN,%20Gilles&rft.genre=article


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