The Contribution of Efflux Pumps in Mycobacterium abscessus Complex Resistance to Clarithromycin

The Contribution of Efflux Pumps in Mycobacterium abscessus Complex Resistance to Clarithromycin

The basis of drug resistance in Mycobacterium abscessus is still poorly understood. Nevertheless, as seen in other microorganisms, the efflux of antimicrobials may also play a role in M. abscessus drug resistance. Here, we investigated the role of efflux pumps in clarithromycin resistance using nine...

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Published in:Antibiotics (Basel) Vol. 8; no. 3; p. 153
Main Authors: Vianna, Júlia S., Machado, Diana, Ramis, Ivy B., Silva, Fábia P., Bierhals, Dienefer V., Abril, Michael Andrés, von Groll, Andrea, Ramos, Daniela F., Lourenço, Maria Cristina S., Viveiros, Miguel, da Silva, Pedro E. Almeida
Format: Journal Article
Language:English
Published: Basel MDPI AG 01-09-2019
MDPI
Subjects:
Antibacterial agents
Antibiotics
Antiinfectives and antibacterials
Antimicrobial agents
Bacteria
Bedaquiline
Biochemistry
Cell membranes
Clarithromycin
Clinical isolates
Drug development
Drug resistance
Efflux
efflux inhibitors
efflux pumps
erm
Fluorimetry
Fluorometry
Gene expression
Genes
Genetic analysis
Genetic research
Genotype & phenotype
Imipenem
Infections
Microbial drug resistance
Microorganisms
Mutation
mutations
Mycobacteria
Mycobacterium abscessus
Physiological aspects
Polymorphism
Pumps
Time
Verapamil
Brazil
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Summary:The basis of drug resistance in Mycobacterium abscessus is still poorly understood. Nevertheless, as seen in other microorganisms, the efflux of antimicrobials may also play a role in M. abscessus drug resistance. Here, we investigated the role of efflux pumps in clarithromycin resistance using nine clinical isolates of M. abscessus complex belonging to the T28 erm(41) sequevar responsible for the inducible resistance to clarithromycin. The strains were characterized by drug susceptibility testing in the presence/absence of the efflux inhibitor verapamil and by genetic analysis of drug-resistance-associated genes. Efflux activity was quantified by real-time fluorometry. Efflux pump gene expression was studied by RT-qPCR upon exposure to clarithromycin. Verapamil increased the susceptibility to clarithromycin from 4- to ≥64-fold. The efflux pump genes MAB_3142 and MAB_1409 were found consistently overexpressed. The results obtained demonstrate that the T28 erm(41) polymorphism is not the sole cause of the inducible clarithromycin resistance in M. abscessus subsp. abscessus or bolletii with efflux activity providing a strong contribution to clarithromycin resistance. These data highlight the need for further studies on M. abscessus efflux response to antimicrobial stress in order to implement more effective therapeutic regimens and guidance in the development of new drugs against these bacteria.
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ISSN:2079-6382
2079-6382
DOI:10.3390/antibiotics8030153