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The contribution of efflux pumps in Mycobacterium abscessus complex resistance to Clarithromycin

2019-09-18Artigo científico Acesso aberto
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dc.contributor.authorVianna, Júlia S
dc.contributor.authorMachado, Diana
dc.contributor.authorRamis, Ivy B
dc.contributor.authorSilva, Fábia P
dc.contributor.authorBierhals, Dienefer V
dc.contributor.authorAbril, Michael Andrés
dc.contributor.authorvon Groll, Andrea
dc.contributor.authorRamos, Daniela F
dc.contributor.authorLourenço, Maria Cristina S
dc.contributor.authorViveiros, Miguel
dc.contributor.authorda Silva, Pedro E Almeida
dc.contributor.institutionTB, HIV and opportunistic diseases and pathogens (THOP)
dc.contributor.institutionGlobal Health and Tropical Medicine (GHTM)
dc.contributor.institutionInstituto de Higiene e Medicina Tropical (IHMT)
dc.contributor.pblMDPI - Multidisciplinary Digital Publishing Institute
dc.date.accessioned2021-05-02T22:44:59Z
dc.date.available2021-05-02T22:44:59Z
dc.date.issued2019-09-18
dc.description.abstractThe 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.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent15
dc.format.extent709114
dc.identifier.doi10.3390/antibiotics8030153
dc.identifier.issn2079-6382
dc.identifier.otherPURE: 14856026
dc.identifier.otherPURE UUID: 9574056d-7a99-43e1-b8cc-a2e1fbbca662
dc.identifier.otherPubMed: 31540480
dc.identifier.otherORCID: /0000-0001-9676-6251/work/63725173
dc.identifier.otherORCID: /0000-0003-2375-2726/work/64041270
dc.identifier.otherPubMedCentral: PMC6784190
dc.identifier.otherScopus: 85073467547
dc.identifier.urihttp://hdl.handle.net/10362/116719
dc.identifier.urlhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6784190/
dc.language.isoeng
dc.peerreviewedyes
dc.subjectEfflux inhibitors
dc.subjectEfflux pumps
dc.subjectErm(41
dc.subjectMutations
dc.subjectMycobacteria
dc.subjectVerapamil
dc.subjectBiochemistry, Genetics and Molecular Biology (miscellaneous)
dc.subjectMicrobiology
dc.subjectInfectious Diseases
dc.subjectSDG 3 - Good Health and Well-being
dc.titleThe contribution of efflux pumps in Mycobacterium abscessus complex resistance to Clarithromycinen
dc.typejournal article
degois.publication.firstPage153
degois.publication.issue3
degois.publication.lastPage168
degois.publication.titleAntibiotics
degois.publication.volume8
dspace.entity.typePublication
rcaap.rightsopenAccess

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