Enhancement of antibiotic activity by efflux inhibitors against multidrug resistant Mycobacterium tuberculosis clinical isolates from Brazil

Detalhes bibliográficos
Autor(a) principal: Coelho, Tatiane
Data de Publicação: 2015
Outros Autores: Machado, Diana, Couto, Isabel, Maschmann, Raquel, Ramos, Daniela, Groll, Andrea von, Rossetti, Maria L., Silva, Pedro A., Viveiros, Miguel
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: https://doi.org/10.3389/fmicb.2015.00330
Resumo: WOS:000354891300001 PMID: 25972842
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spelling Enhancement of antibiotic activity by efflux inhibitors against multidrug resistant Mycobacterium tuberculosis clinical isolates from BrazilCheckerboardDrug resistanceFluorometryFractional inhibitory concentrationTEMATuberculosisMicrobiologyMicrobiology (medical)SDG 3 - Good Health and Well-beingWOS:000354891300001 PMID: 25972842Drug resistant tuberculosis continues to increase and new approaches for its treatment are necessary. The identification of M. tuberculosis clinical isolates presenting efflux as part of their resistant phenotype has a major impact in tuberculosis treatment. In this work, we used a checkerboard procedure combined with the tetrazolium microplate-based assay (TEMA) to study single combinations between antituberculosis drugs and efflux inhibitors (EIs) against multidrug resistant M. tuberculosis clinical isolates using the fully susceptible strain H37Rv as reference. Efflux activity was studied on a real-time basis by a fluorometric method that uses ethidium bromide as efflux substrate. Quantification of efflux pump genes mRNA transcriptional levels were performed by RT-qPCR. The fractional inhibitory concentrations (FIC) indicated synergistic activity for the interactions between isoniazid, rifampicin, amikacin, ofloxacin, and ethidium bromide plus the EIs verapamil, thioridazine and chlorpromazine. The FICs ranged from 0.25, indicating a four-fold reduction on the MICs, to 0.015, 64-fold reduction. The detection of active efflux by real-time fluorometry showed that all strains presented intrinsic efflux activity that contributes to the overall resistance which can be inhibited in the presence of the EIs. The quantification of the mRNA levels of the most important efflux pump genes on these strains shows that they are intrinsically predisposed to expel toxic compounds as the exposure to subinhibitory concentrations of antibiotics were not necessary to increase the pump mRNA levels when compared with the non-exposed counterpart. The results obtained in this study confirm that the intrinsic efflux activity contributes to the overall resistance in multidrug resistant clinical isolates of M. tuberculosis and that the inhibition of efflux pumps by the EIs can enhance the clinical effect of antibiotics that are their substrates.Instituto de Higiene e Medicina Tropical (IHMT)TB, HIV and opportunistic diseases and pathogens (THOP)Global Health and Tropical Medicine (GHTM)RUNCoelho, TatianeMachado, DianaCouto, IsabelMaschmann, RaquelRamos, DanielaGroll, Andrea vonRossetti, Maria L.Silva, Pedro A.Viveiros, Miguel2018-05-14T22:01:31Z2015-04-282015-04-28T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article12application/pdfhttps://doi.org/10.3389/fmicb.2015.00330eng1664-302XPURE: 1644836http://www.scopus.com/inward/record.url?scp=84930941347&partnerID=8YFLogxKhttps://doi.org/10.3389/fmicb.2015.00330info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T04:20:27Zoai:run.unl.pt:10362/36925Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:30:42.077537Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Enhancement of antibiotic activity by efflux inhibitors against multidrug resistant Mycobacterium tuberculosis clinical isolates from Brazil
title Enhancement of antibiotic activity by efflux inhibitors against multidrug resistant Mycobacterium tuberculosis clinical isolates from Brazil
spellingShingle Enhancement of antibiotic activity by efflux inhibitors against multidrug resistant Mycobacterium tuberculosis clinical isolates from Brazil
Coelho, Tatiane
Checkerboard
Drug resistance
Fluorometry
Fractional inhibitory concentration
TEMA
Tuberculosis
Microbiology
Microbiology (medical)
SDG 3 - Good Health and Well-being
title_short Enhancement of antibiotic activity by efflux inhibitors against multidrug resistant Mycobacterium tuberculosis clinical isolates from Brazil
title_full Enhancement of antibiotic activity by efflux inhibitors against multidrug resistant Mycobacterium tuberculosis clinical isolates from Brazil
title_fullStr Enhancement of antibiotic activity by efflux inhibitors against multidrug resistant Mycobacterium tuberculosis clinical isolates from Brazil
title_full_unstemmed Enhancement of antibiotic activity by efflux inhibitors against multidrug resistant Mycobacterium tuberculosis clinical isolates from Brazil
title_sort Enhancement of antibiotic activity by efflux inhibitors against multidrug resistant Mycobacterium tuberculosis clinical isolates from Brazil
author Coelho, Tatiane
author_facet Coelho, Tatiane
Machado, Diana
Couto, Isabel
Maschmann, Raquel
Ramos, Daniela
Groll, Andrea von
Rossetti, Maria L.
Silva, Pedro A.
Viveiros, Miguel
author_role author
author2 Machado, Diana
Couto, Isabel
Maschmann, Raquel
Ramos, Daniela
Groll, Andrea von
Rossetti, Maria L.
Silva, Pedro A.
Viveiros, Miguel
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Instituto de Higiene e Medicina Tropical (IHMT)
TB, HIV and opportunistic diseases and pathogens (THOP)
Global Health and Tropical Medicine (GHTM)
RUN
dc.contributor.author.fl_str_mv Coelho, Tatiane
Machado, Diana
Couto, Isabel
Maschmann, Raquel
Ramos, Daniela
Groll, Andrea von
Rossetti, Maria L.
Silva, Pedro A.
Viveiros, Miguel
dc.subject.por.fl_str_mv Checkerboard
Drug resistance
Fluorometry
Fractional inhibitory concentration
TEMA
Tuberculosis
Microbiology
Microbiology (medical)
SDG 3 - Good Health and Well-being
topic Checkerboard
Drug resistance
Fluorometry
Fractional inhibitory concentration
TEMA
Tuberculosis
Microbiology
Microbiology (medical)
SDG 3 - Good Health and Well-being
description WOS:000354891300001 PMID: 25972842
publishDate 2015
dc.date.none.fl_str_mv 2015-04-28
2015-04-28T00:00:00Z
2018-05-14T22:01:31Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv https://doi.org/10.3389/fmicb.2015.00330
url https://doi.org/10.3389/fmicb.2015.00330
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 1664-302X
PURE: 1644836
http://www.scopus.com/inward/record.url?scp=84930941347&partnerID=8YFLogxK
https://doi.org/10.3389/fmicb.2015.00330
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 12
application/pdf
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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