Constitutive Activation of MexT by Amino Acid Substitutions Results in MexEF-OprN Overproduction in Clinical Isolates of Pseudomonas aeruginosa-Reference-Cited by-同舟云学术

Constitutive Activation of MexT by Amino Acid Substitutions Results in MexEF-OprN Overproduction in Clinical Isolates of Pseudomonas aeruginosa

Published:2018-05 Issue:5 Volume:62 Page:
ISSN:0066-4804
Container-title:Antimicrobial Agents and Chemotherapy
language:en
Short-container-title:Antimicrob Agents Chemother

Author:

Juarez Paulo¹²^ORCID,Broutin Isabelle³,Bordi Christophe⁴,Plésiat Patrick¹⁵,Llanes Catherine¹

Affiliation:

1. UMR CNRS 6249 Chrono-Environnement, Laboratoire de Bactériologie, Université de Bourgogne Franche-Comté, Besançon, France

2. Research and Development Department, Smaltis SAS, Besançon, France

3. UMR CNRS 8015, Université Paris Descartes, Sorbonne Paris Cité, Laboratoire de Cristallographie et RMN Biologiques, Faculté de Pharmacie, Paris, France

4. LISM, IMM, Aix-Marseille Université and CNRS, Marseille, France

5. Centre National de Référence de la Résistance aux Antibiotiques, Centre Hospitalier Universitaire Jean Minjoz, Besançon, France

Abstract

ABSTRACT When overproduced, the multidrug efflux system MexEF-OprN increases the resistance of Pseudomonas aeruginosa to fluoroquinolones, chloramphenicol, and trimethoprim. In this work, we demonstrate that gain-of-function mutations in the regulatory gene mexT result in oligomerization of the LysR regulator MexT, constitutive upregulation of the efflux pump, and increased resistance in clinical isolates.

Funder

Ministère de l'Enseignement Supérieur et de la Recherche

Vaincre la Mucoviscidose

Association Grégory Lemarchal

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

Link

https://journals.asm.org/doi/pdf/10.1128/AAC.02445-17

Reference19 articles.

1. The Challenge of Efflux-Mediated Antibiotic Resistance in Gram-Negative Bacteria