• Skip to primary navigation
  • Skip to main content
  • Skip to footer
  • Biblioteca
  • Museu
  • Pessoal
    • Webmail
    • Área de Docentes
    • Área de Não-Docentes
  • Estudantes
    • Webmail
    • Moodle
    • NetP@
    • Escola Doutoral
    • Serviços Académicos
    • Trabalhar no IHMT

IHMT

Instituto de Higiene e Medicina Tropical

  • O Instituto
    • Missão
    • Mensagem do Diretor
    • Órgãos de governo
    • Docentes e investigadores
    • Portal de Denúncias UNL
  • Ensino
    • Mestrados
    • Doutoramentos
    • Cursos de Especialização
    • Formação transversal
    • Cursos de Curta Duração
    • Ensino à Distância
    • Apoio ao Desenvolvimento
    • Serviços académicos
    • NOVA Open Academy
  • Investigação
    • Centro GHTM
    • Unidades de Ensino e de Investigação (UEI)
      • Unidade de Clínica Tropical
      • Unidade de Microbiologia Médica
      • Unidade de Parasitologia Médica
      • Unidade de Saúde Pública Global
      • Serviço de Apoio à Ciência e Comunidade
    • Biobanco
    • BLOODless
    • Centro Colaborador OMS
    • Publicações
  • Serviços e gestão
    • Biblioteca
    • Sistema de Qualidade
    • Estatutos e regulamentos
    • Plano de Atividades
    • Relatório de Atividades
    • Relatório de Gestão
    • Contratos públicos
    • Recursos humanos
      • Concursos e bolsas
        • Concursos – Docentes e Investigadores
        • Concursos – Não Docentes e Não Investigadores
        • Bolsas de Investigação
      • Contratos
      • Avaliação de Desempenho
        • Ciclo Avaliativo
          • Biénio 2021-2022
          • Biénio 2023-2024
        • Conselho Coordenador de Avaliação
        • Comissão Paritária
      • Mobilidade
      • Listas Nominativas
  • Doenças Tropicais
    • Consulta do Viajante
    • Dossiês Informativos
    • Glossário
    • Museu
    • Vídeos
    • MosquitoWeb
  • Comunidade
    • Cooperação e Desenvolvimento
    • Formação
    • Parcerias
  • Contactos
  • Candidaturas
  • pt
    • pt
    • en
Home / Publicações / Contribution of efflux activity to isoniazid resistance in the Mycobacterium tuberculosis complex.

Contribution of efflux activity to isoniazid resistance in the Mycobacterium tuberculosis complex.

  • Autores: Amaral L, Couto I, Machado D, Rodrigues L, Viveiros M
  • Ano de Publicação: 2012
  • Journal: Genetics and Evolution
  • Link: http://www.ncbi.nlm.nih.gov/pubmed/?term=Contribution+of+efflux+activity+to+isoniazid+resistance+in+the+Mycobacterium+tuberculosis+complex.+Infection

Resistance to isoniazid (INH), one of the main drugs used in tuberculosis (TB) therapy, is mostly due to chromosomal mutations in target genes. However, approximately 20-30% of INH resistant Mycobacterium tuberculosis isolates do not have mutations in any of the genes associated with INH resistance. This suggests that other mechanism(s) may be involved, namely efflux pump systems capable of extruding the drug to the exterior of the cell. In a previous work, we have induced clinical INH susceptible M. tuberculosis isolates and the H37Rv reference strain to high-level resistance to INH, by gradual exposure to increasing concentrations of this drug. In the present study, we have characterized these strains and Mycobacterium bovis BCG induced to INH resistance with respect to their efflux activity and its contribution to INH resistance using the following approach: determination of the susceptibility to INH in the presence and absence of the efflux inhibitors (EIs) chlorpromazine, thioridazine and verapamil; evaluation of efflux activity by a semi-automated fluorometric method; and quantification of the expression level of genes coding for efflux pumps by real-time RT-qPCR. The EIs decreased INH resistance in the INH induced strains, in particular verapamil promoted a reversal of resistance in some of the strains tested. The induced strains presented an increased efflux activity that was inhibited by the EIs and showed overexpression of the efflux pump genes efpA, mmpL7, mmr, p55 and the Tap-like gene Rv1258c. Altogether, these results correlate efflux activity with INH resistance and demonstrate that efflux pumps play an important role in acquired INH resistance in M. tuberculosis complex. The development of EIs that can restore the antimicrobial activity of the antibiotic subject to efflux is an approach that can be useful in order to prevent the emergence of this resistance and guide the development of new effective anti-TB therapeutical approaches.
Copyright © 2011 Elsevier B.V. All rights reserved.

Contribution of efflux activity to isoniazid resistance in the Mycobacterium tuberculosis complex.

  • Autores: Amaral L, Couto I, Machado D, Rodrigues L, Viveiros M
  • Ano de Publicação: 2012
  • Journal: Genetics and Evolution
  • Link: http://www.ncbi.nlm.nih.gov/pubmed/?term=Contribution+of+efflux+activity+to+isoniazid+resistance+in+the+Mycobacterium+tuberculosis+complex.+Infection

Resistance to isoniazid (INH), one of the main drugs used in tuberculosis (TB) therapy, is mostly due to chromosomal mutations in target genes. However, approximately 20-30% of INH resistant Mycobacterium tuberculosis isolates do not have mutations in any of the genes associated with INH resistance. This suggests that other mechanism(s) may be involved, namely efflux pump systems capable of extruding the drug to the exterior of the cell. In a previous work, we have induced clinical INH susceptible M. tuberculosis isolates and the H37Rv reference strain to high-level resistance to INH, by gradual exposure to increasing concentrations of this drug. In the present study, we have characterized these strains and Mycobacterium bovis BCG induced to INH resistance with respect to their efflux activity and its contribution to INH resistance using the following approach: determination of the susceptibility to INH in the presence and absence of the efflux inhibitors (EIs) chlorpromazine, thioridazine and verapamil; evaluation of efflux activity by a semi-automated fluorometric method; and quantification of the expression level of genes coding for efflux pumps by real-time RT-qPCR. The EIs decreased INH resistance in the INH induced strains, in particular verapamil promoted a reversal of resistance in some of the strains tested. The induced strains presented an increased efflux activity that was inhibited by the EIs and showed overexpression of the efflux pump genes efpA, mmpL7, mmr, p55 and the Tap-like gene Rv1258c. Altogether, these results correlate efflux activity with INH resistance and demonstrate that efflux pumps play an important role in acquired INH resistance in M. tuberculosis complex. The development of EIs that can restore the antimicrobial activity of the antibiotic subject to efflux is an approach that can be useful in order to prevent the emergence of this resistance and guide the development of new effective anti-TB therapeutical approaches.
Copyright © 2011 Elsevier B.V. All rights reserved.

Footer

INSTITUTO DE HIGIENE E
MEDICINA TROPICAL
UNIVERSIDADE NOVA DE LISBOA
Rua da Junqueira, 100 1349-008 Lisboa
T +351 213 652 600
geral@ihmt.unl.pt

Consulta do Viajante e Medicina Tropical
T +351 213 652 630
T +351 213 652 690
T +351 91 182 37 48
T +351 91 182 44 67
medicina.viagens@ihmt.unl.pt

  • Ensino
  • Investigação
  • Medicina Tropical
  • Cooperação
  • Portal de Denúncias UNL

NOVA University of Lisbon Logo

Siga-nos

  • Facebook
  • Instagram
  • LinkedIn
  • Twitter
  • YouTube

Receber a “newsletter”

© Copyright 2025 IHMT-UNL Todos os Direitos Reservados.
  • Universidade Nova de Lisboa
  • Fundação para a Ciência e a Tecnologia

    UIDB/04413/2020
    UIDP/04413/2020

We use cookies to ensure that we give you the best experience on our website. If you continue to use this site we will assume that you are happy with it.Ok