The TetR Family Transcription Factor MAB_2299c Regulates the Expression of Two Distinct MmpS-MmpL Efflux Pumps Involved in Cross-Resistance to Clofazimine and Bedaquiline in Mycobacterium abscessus

Ana Victoria Gutiérrez; Matthias Richard; Françoise Roquet-Banères; Albertus Viljoen; Laurent Kremer

doi:10.1128/AAC.01000-19

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The TetR Family Transcription Factor MAB_2299c Regulates the Expression of Two Distinct MmpS-MmpL Efflux Pumps Involved in Cross-Resistance to Clofazimine and Bedaquiline in Mycobacterium abscessus

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The TetR Family Transcription Factor MAB_2299c Regulates the Expression of Two Distinct MmpS-MmpL Efflux Pumps Involved in Cross-Resistance to Clofazimine and Bedaquiline in Mycobacterium abscessus

Ana Victoria Gutiérrez, Matthias Richard, Françoise Roquet-Banères, Albertus Viljoen et Laurent Kremer

Antimicrobial Agents and Chemotherapy, Vol.63(10)

10/2019

DOI: https://doi.org/10.1128/AAC.01000-19

PMCID: PMC6761555

PMID: 31332077

Résumé

EMSA

efflux pumps

MmpL

Mycobacterium abscessus

TetR regulator

bedaquiline

clofazimine

drug resistance mechanisms

Antitubercular Agents / pharmacology*

Bacterial Proteins / genetics

Microbial Sensitivity Tests

Mycobacterium abscessus / drug effects*

Mycobacterium abscessus / metabolism*

Real-Time Polymerase Chain Reaction

THP-1 Cells

Transcription Factors / genetics

Transcription Factors / metabolism*

Bacterial Proteins / metabolism*

Clofazimine / pharmacology*

Diarylquinolines / pharmacology*

Drug Resistance, Bacterial / genetics

Electrophoretic Mobility Shift Assay

Gene Expression Regulation / drug effects

Gene Expression Regulation / genetics

Humans

Mycobacterium abscessus is a human pathogen responsible for severe respiratory infections, particularly in patients with underlying lung disorders. Notorious for being highly resistant to most antimicrobials, new therapeutic approaches are needed to successfully treat M. abscessus -infected patients. Clofazimine (CFZ) and bedaquiline (BDQ) are two antibiotics used for the treatment of multidrug-resistant tuberculosis and are considered alternatives for the treatment of M. abscessus pulmonary disease.

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Titre: The TetR Family Transcription Factor MAB_2299c Regulates the Expression of Two Distinct MmpS-MmpL Efflux Pumps Involved in Cross-Resistance to Clofazimine and Bedaquiline in Mycobacterium abscessus
Créateurs - sans rôle: Ana Victoria Gutiérrez - Université de Montpellier, Institut de Recherche en Infectiologie de Montpellier - IRIM
Matthias Richard - Université de Montpellier, Institut de Recherche en Infectiologie de Montpellier - IRIM
Françoise Roquet-Banères - Université de Montpellier, Institut de Recherche en Infectiologie de Montpellier - IRIM
Albertus Viljoen - Université de Montpellier, Institut de Recherche en Infectiologie de Montpellier - IRIM
Laurent Kremer - Université de Montpellier, Institut de Recherche en Infectiologie de Montpellier - IRIM
Détails de publication: Antimicrobial Agents and Chemotherapy, Vol.63(10)
Note de subvention: Fondation pour la Recherche Médicale (FRM) (grant number DEQ20150331719 to L.K.; grant number ECO20160736031 to M.R.)
Identifiants: 99151264709311
Unité académique: Institut de Recherche en Infectiologie de Montpellier - IRIM
Langue: English
Type de ressource: Journal article
Champs locaux: hal-05311092