The Contribution of efflux pumps in Mycobacterium abscessus complex resistance to clarithromycin

Detalhes bibliográficos
Autor(a) principal: Vianna, Júlia S.
Data de Publicação: 2019
Outros Autores: Machado, Diana, Ramis, Ivy B., Silva, Fábia P., Bierhals, Dienefer V., Abril, Michael Andrés, Groll, Andrea von, Ramos, Daniela F., Lourenço, Maria Cristina S., Viveiros, Miguel, Silva, Pedro E. Almeida da
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/36952
Resumo: Universidade Federal de Rio Grande. Núcleo de Pesquisas em Microbiologia Médica. Rio Grande, RS, Brasil.
id CRUZ_4a7355679577e706784c60c880303c8e
oai_identifier_str oai:www.arca.fiocruz.br:icict/36952
network_acronym_str CRUZ
network_name_str Repositório Institucional da FIOCRUZ (ARCA)
repository_id_str 2135
spelling Vianna, Júlia S.Machado, DianaRamis, Ivy B.Silva, Fábia P.Bierhals, Dienefer V.Abril, Michael AndrésGroll, Andrea vonRamos, Daniela F.Lourenço, Maria Cristina S.Viveiros, MiguelSilva, Pedro E. Almeida da2019-11-08T12:27:38Z2019-11-08T12:27:38Z2019VIANNA, Júlia S. et al. The contribution of efflux pumps in Mycobacterium abscessus complex resistance to clarithromycin. Antibiotics, v. 8, p. 1-15, 2019.2079-6382https://www.arca.fiocruz.br/handle/icict/3695210.3390/antibiotics80301532079-6382engMDPIThe Contribution of efflux pumps in Mycobacterium abscessus complex resistance to clarithromycininfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversidade Federal de Rio Grande. Núcleo de Pesquisas em Microbiologia Médica. Rio Grande, RS, Brasil.Universidade Nova de Lisboa. Instituto de Higiene e Medicina Tropical. Global Health and Tropical Medicine. Lisboa, Portugal.Universidade Federal de Rio Grande. Núcleo de Pesquisas em Microbiologia Médica. Rio Grande, RS, Brasil.Universidade Federal de Rio Grande. Núcleo de Pesquisas em Microbiologia Médica. Rio Grande, RS, Brasil.Universidade Federal de Rio Grande. Núcleo de Pesquisas em Microbiologia Médica. Rio Grande, RS, Brasil.Universidade Federal de Rio Grande. Núcleo de Pesquisas em Microbiologia Médica. Rio Grande, RS, Brasil.Universidade Federal de Rio Grande. Núcleo de Pesquisas em Microbiologia Médica. Rio Grande, RS, Brasil.Universidade Federal de Rio Grande. Núcleo de Pesquisas em Microbiologia Médica. Rio Grande, RS, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.Universidade Nova de Lisboa. Instituto de Higiene e Medicina Tropical. Global Health and Tropical Medicine. Lisboa, Portugal.Universidade Federal de Rio Grande. Núcleo de Pesquisas em Microbiologia Médica. Rio Grande, RS, Brasil.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.Efflux inhibitorsEfflux pumpsErm(41)MutationsMycobacteriaVerapamilinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-83104https://www.arca.fiocruz.br/bitstream/icict/36952/1/license.txt79178e5f2a0eb066867a274556814938MD51ORIGINALve_Vianna_Júlia_etal_INI_2019.pdfve_Vianna_Júlia_etal_INI_2019.pdfapplication/pdf709114https://www.arca.fiocruz.br/bitstream/icict/36952/2/ve_Vianna_J%c3%balia_etal_INI_2019.pdfb1ed5809148e8413da3e93792838a4faMD52TEXTve_Vianna_Júlia_etal_INI_2019.pdf.txtve_Vianna_Júlia_etal_INI_2019.pdf.txtExtracted texttext/plain63306https://www.arca.fiocruz.br/bitstream/icict/36952/3/ve_Vianna_J%c3%balia_etal_INI_2019.pdf.txt69d51ec923fc2281a4dadf6543a68123MD53icict/369522019-11-09 02:01:36.67oai:www.arca.fiocruz.br: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Repositório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352019-11-09T05:01:36Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false
dc.title.pt_BR.fl_str_mv The Contribution of efflux pumps in Mycobacterium abscessus complex resistance to clarithromycin
title The Contribution of efflux pumps in Mycobacterium abscessus complex resistance to clarithromycin
spellingShingle The Contribution of efflux pumps in Mycobacterium abscessus complex resistance to clarithromycin
Vianna, Júlia S.
Efflux inhibitors
Efflux pumps
Erm(41)
Mutations
Mycobacteria
Verapamil
title_short The Contribution of efflux pumps in Mycobacterium abscessus complex resistance to clarithromycin
title_full The Contribution of efflux pumps in Mycobacterium abscessus complex resistance to clarithromycin
title_fullStr The Contribution of efflux pumps in Mycobacterium abscessus complex resistance to clarithromycin
title_full_unstemmed The Contribution of efflux pumps in Mycobacterium abscessus complex resistance to clarithromycin
title_sort The Contribution of efflux pumps in Mycobacterium abscessus complex resistance to clarithromycin
author Vianna, Júlia S.
author_facet Vianna, Júlia S.
Machado, Diana
Ramis, Ivy B.
Silva, Fábia P.
Bierhals, Dienefer V.
Abril, Michael Andrés
Groll, Andrea von
Ramos, Daniela F.
Lourenço, Maria Cristina S.
Viveiros, Miguel
Silva, Pedro E. Almeida da
author_role author
author2 Machado, Diana
Ramis, Ivy B.
Silva, Fábia P.
Bierhals, Dienefer V.
Abril, Michael Andrés
Groll, Andrea von
Ramos, Daniela F.
Lourenço, Maria Cristina S.
Viveiros, Miguel
Silva, Pedro E. Almeida da
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Vianna, Júlia S.
Machado, Diana
Ramis, Ivy B.
Silva, Fábia P.
Bierhals, Dienefer V.
Abril, Michael Andrés
Groll, Andrea von
Ramos, Daniela F.
Lourenço, Maria Cristina S.
Viveiros, Miguel
Silva, Pedro E. Almeida da
dc.subject.en.pt_BR.fl_str_mv Efflux inhibitors
Efflux pumps
Erm(41)
Mutations
Mycobacteria
Verapamil
topic Efflux inhibitors
Efflux pumps
Erm(41)
Mutations
Mycobacteria
Verapamil
description Universidade Federal de Rio Grande. Núcleo de Pesquisas em Microbiologia Médica. Rio Grande, RS, Brasil.
publishDate 2019
dc.date.accessioned.fl_str_mv 2019-11-08T12:27:38Z
dc.date.available.fl_str_mv 2019-11-08T12:27:38Z
dc.date.issued.fl_str_mv 2019
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.citation.fl_str_mv VIANNA, Júlia S. et al. The contribution of efflux pumps in Mycobacterium abscessus complex resistance to clarithromycin. Antibiotics, v. 8, p. 1-15, 2019.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/36952
dc.identifier.issn.pt_BR.fl_str_mv 2079-6382
dc.identifier.doi.none.fl_str_mv 10.3390/antibiotics8030153
dc.identifier.eissn.none.fl_str_mv 2079-6382
identifier_str_mv VIANNA, Júlia S. et al. The contribution of efflux pumps in Mycobacterium abscessus complex resistance to clarithromycin. Antibiotics, v. 8, p. 1-15, 2019.
2079-6382
10.3390/antibiotics8030153
url https://www.arca.fiocruz.br/handle/icict/36952
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
bitstream.url.fl_str_mv https://www.arca.fiocruz.br/bitstream/icict/36952/1/license.txt
https://www.arca.fiocruz.br/bitstream/icict/36952/2/ve_Vianna_J%c3%balia_etal_INI_2019.pdf
https://www.arca.fiocruz.br/bitstream/icict/36952/3/ve_Vianna_J%c3%balia_etal_INI_2019.pdf.txt
bitstream.checksum.fl_str_mv 79178e5f2a0eb066867a274556814938
b1ed5809148e8413da3e93792838a4fa
69d51ec923fc2281a4dadf6543a68123
bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
MD5
repository.name.fl_str_mv Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)
repository.mail.fl_str_mv repositorio.arca@fiocruz.br
_version_ 1798324874557521920