Cargando…

Antibiotic export by MexB multidrug efflux transporter is allosterically controlled by a MexA-OprM chaperone-like complex

The tripartite multidrug efflux system MexAB-OprM is a major actor in Pseudomonas aeruginosa antibiotic resistance by exporting a large variety of antimicrobial compounds. Crystal structures of MexB and of its Escherichia coli homolog AcrB had revealed asymmetric trimers depicting a directional drug...

Descripción completa

Detalles Bibliográficos
Autores principales: Glavier, Marie, Puvanendran, Dhenesh, Salvador, Dimitri, Decossas, Marion, Phan, Gilles, Garnier, Cyril, Frezza, Elisa, Cece, Quentin, Schoehn, Guy, Picard, Martin, Taveau, Jean-Christophe, Daury, Laetitia, Broutin, Isabelle, Lambert, Olivier
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532149/
https://www.ncbi.nlm.nih.gov/pubmed/33009415
http://dx.doi.org/10.1038/s41467-020-18770-5
_version_ 1783589864832237568
author Glavier, Marie
Puvanendran, Dhenesh
Salvador, Dimitri
Decossas, Marion
Phan, Gilles
Garnier, Cyril
Frezza, Elisa
Cece, Quentin
Schoehn, Guy
Picard, Martin
Taveau, Jean-Christophe
Daury, Laetitia
Broutin, Isabelle
Lambert, Olivier
author_facet Glavier, Marie
Puvanendran, Dhenesh
Salvador, Dimitri
Decossas, Marion
Phan, Gilles
Garnier, Cyril
Frezza, Elisa
Cece, Quentin
Schoehn, Guy
Picard, Martin
Taveau, Jean-Christophe
Daury, Laetitia
Broutin, Isabelle
Lambert, Olivier
author_sort Glavier, Marie
collection PubMed
description The tripartite multidrug efflux system MexAB-OprM is a major actor in Pseudomonas aeruginosa antibiotic resistance by exporting a large variety of antimicrobial compounds. Crystal structures of MexB and of its Escherichia coli homolog AcrB had revealed asymmetric trimers depicting a directional drug pathway by a conformational interconversion (from Loose and Tight binding pockets to Open gate (LTO) for drug exit). It remains unclear how MexB acquires its LTO form. Here by performing functional and cryo-EM structural investigations of MexB at various stages of the assembly process, we unveil that MexB inserted in lipid membrane is not set for active transport because it displays an inactive LTC form with a Closed exit gate. In the tripartite complex, OprM and MexA form a corset-like platform that converts MexB into the active form. Our findings shed new light on the resistance nodulation cell division (RND) cognate partners which act as allosteric factors eliciting the functional drug extrusion.
format Online
Article
Text
id pubmed-7532149
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-75321492020-10-19 Antibiotic export by MexB multidrug efflux transporter is allosterically controlled by a MexA-OprM chaperone-like complex Glavier, Marie Puvanendran, Dhenesh Salvador, Dimitri Decossas, Marion Phan, Gilles Garnier, Cyril Frezza, Elisa Cece, Quentin Schoehn, Guy Picard, Martin Taveau, Jean-Christophe Daury, Laetitia Broutin, Isabelle Lambert, Olivier Nat Commun Article The tripartite multidrug efflux system MexAB-OprM is a major actor in Pseudomonas aeruginosa antibiotic resistance by exporting a large variety of antimicrobial compounds. Crystal structures of MexB and of its Escherichia coli homolog AcrB had revealed asymmetric trimers depicting a directional drug pathway by a conformational interconversion (from Loose and Tight binding pockets to Open gate (LTO) for drug exit). It remains unclear how MexB acquires its LTO form. Here by performing functional and cryo-EM structural investigations of MexB at various stages of the assembly process, we unveil that MexB inserted in lipid membrane is not set for active transport because it displays an inactive LTC form with a Closed exit gate. In the tripartite complex, OprM and MexA form a corset-like platform that converts MexB into the active form. Our findings shed new light on the resistance nodulation cell division (RND) cognate partners which act as allosteric factors eliciting the functional drug extrusion. Nature Publishing Group UK 2020-10-02 /pmc/articles/PMC7532149/ /pubmed/33009415 http://dx.doi.org/10.1038/s41467-020-18770-5 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Glavier, Marie
Puvanendran, Dhenesh
Salvador, Dimitri
Decossas, Marion
Phan, Gilles
Garnier, Cyril
Frezza, Elisa
Cece, Quentin
Schoehn, Guy
Picard, Martin
Taveau, Jean-Christophe
Daury, Laetitia
Broutin, Isabelle
Lambert, Olivier
Antibiotic export by MexB multidrug efflux transporter is allosterically controlled by a MexA-OprM chaperone-like complex
title Antibiotic export by MexB multidrug efflux transporter is allosterically controlled by a MexA-OprM chaperone-like complex
title_full Antibiotic export by MexB multidrug efflux transporter is allosterically controlled by a MexA-OprM chaperone-like complex
title_fullStr Antibiotic export by MexB multidrug efflux transporter is allosterically controlled by a MexA-OprM chaperone-like complex
title_full_unstemmed Antibiotic export by MexB multidrug efflux transporter is allosterically controlled by a MexA-OprM chaperone-like complex
title_short Antibiotic export by MexB multidrug efflux transporter is allosterically controlled by a MexA-OprM chaperone-like complex
title_sort antibiotic export by mexb multidrug efflux transporter is allosterically controlled by a mexa-oprm chaperone-like complex
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532149/
https://www.ncbi.nlm.nih.gov/pubmed/33009415
http://dx.doi.org/10.1038/s41467-020-18770-5
work_keys_str_mv AT glaviermarie antibioticexportbymexbmultidrugeffluxtransporterisallostericallycontrolledbyamexaoprmchaperonelikecomplex
AT puvanendrandhenesh antibioticexportbymexbmultidrugeffluxtransporterisallostericallycontrolledbyamexaoprmchaperonelikecomplex
AT salvadordimitri antibioticexportbymexbmultidrugeffluxtransporterisallostericallycontrolledbyamexaoprmchaperonelikecomplex
AT decossasmarion antibioticexportbymexbmultidrugeffluxtransporterisallostericallycontrolledbyamexaoprmchaperonelikecomplex
AT phangilles antibioticexportbymexbmultidrugeffluxtransporterisallostericallycontrolledbyamexaoprmchaperonelikecomplex
AT garniercyril antibioticexportbymexbmultidrugeffluxtransporterisallostericallycontrolledbyamexaoprmchaperonelikecomplex
AT frezzaelisa antibioticexportbymexbmultidrugeffluxtransporterisallostericallycontrolledbyamexaoprmchaperonelikecomplex
AT cecequentin antibioticexportbymexbmultidrugeffluxtransporterisallostericallycontrolledbyamexaoprmchaperonelikecomplex
AT schoehnguy antibioticexportbymexbmultidrugeffluxtransporterisallostericallycontrolledbyamexaoprmchaperonelikecomplex
AT picardmartin antibioticexportbymexbmultidrugeffluxtransporterisallostericallycontrolledbyamexaoprmchaperonelikecomplex
AT taveaujeanchristophe antibioticexportbymexbmultidrugeffluxtransporterisallostericallycontrolledbyamexaoprmchaperonelikecomplex
AT daurylaetitia antibioticexportbymexbmultidrugeffluxtransporterisallostericallycontrolledbyamexaoprmchaperonelikecomplex
AT broutinisabelle antibioticexportbymexbmultidrugeffluxtransporterisallostericallycontrolledbyamexaoprmchaperonelikecomplex
AT lambertolivier antibioticexportbymexbmultidrugeffluxtransporterisallostericallycontrolledbyamexaoprmchaperonelikecomplex