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, von Groll, Andrea, Ramos, Daniela F, Lourenço, Maria Cristina S, Viveiros, Miguel, da Silva, Pedro E Almeida
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/116719
Resumo: 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.
id RCAP_8d8e2bf13784288977c09722c12f119e
oai_identifier_str oai:run.unl.pt:10362/116719
network_acronym_str RCAP
network_name_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository_id_str 7160
spelling The contribution of efflux pumps in Mycobacterium abscessus complex resistance to ClarithromycinEfflux inhibitorsEfflux pumpsErm(41MutationsMycobacteriaVerapamilBiochemistry, Genetics and Molecular Biology (miscellaneous)MicrobiologyInfectious DiseasesSDG 3 - Good Health and Well-beingThe 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.TB, HIV and opportunistic diseases and pathogens (THOP)Global Health and Tropical Medicine (GHTM)Instituto de Higiene e Medicina Tropical (IHMT)RUNVianna, Júlia SMachado, DianaRamis, Ivy BSilva, Fábia PBierhals, Dienefer VAbril, Michael Andrésvon Groll, AndreaRamos, Daniela FLourenço, Maria Cristina SViveiros, Miguelda Silva, Pedro E Almeida2021-05-02T22:44:59Z2019-09-182019-09-18T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article15application/pdfhttp://hdl.handle.net/10362/116719eng2079-6382PURE: 14856026https://doi.org/10.3390/antibiotics8030153info: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:RCAAP2024-03-11T04:59:25Zoai:run.unl.pt:10362/116719Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:43:13.875787Repositório 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 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
Biochemistry, Genetics and Molecular Biology (miscellaneous)
Microbiology
Infectious Diseases
SDG 3 - Good Health and Well-being
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
von Groll, Andrea
Ramos, Daniela F
Lourenço, Maria Cristina S
Viveiros, Miguel
da Silva, Pedro E Almeida
author_role author
author2 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
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv TB, HIV and opportunistic diseases and pathogens (THOP)
Global Health and Tropical Medicine (GHTM)
Instituto de Higiene e Medicina Tropical (IHMT)
RUN
dc.contributor.author.fl_str_mv 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
dc.subject.por.fl_str_mv Efflux inhibitors
Efflux pumps
Erm(41
Mutations
Mycobacteria
Verapamil
Biochemistry, Genetics and Molecular Biology (miscellaneous)
Microbiology
Infectious Diseases
SDG 3 - Good Health and Well-being
topic Efflux inhibitors
Efflux pumps
Erm(41
Mutations
Mycobacteria
Verapamil
Biochemistry, Genetics and Molecular Biology (miscellaneous)
Microbiology
Infectious Diseases
SDG 3 - Good Health and Well-being
description 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.
publishDate 2019
dc.date.none.fl_str_mv 2019-09-18
2019-09-18T00:00:00Z
2021-05-02T22:44:59Z
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 http://hdl.handle.net/10362/116719
url http://hdl.handle.net/10362/116719
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 2079-6382
PURE: 14856026
https://doi.org/10.3390/antibiotics8030153
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 15
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
repository.mail.fl_str_mv
_version_ 1799138042542292992