GHTM

Global Health and Tropical Medicine

  • GHTM
    • Vision
    • Mission
    • Governance
    • Scientific Advisory Board
  • News
    • Outreach
    • Events
      • GHTM Sessions
      • Workshops
    • Articles
    • Jobs
  • Research
    • Cross-cutting issues
      • Global Pathogen Dispersion and Population Mobility
      • Drug Discovery and Drug Resistance
      • Diagnostics
      • Public Health Information
      • Fair Research Partnerships
    • Research Groups
      • PPS – Population health, policies and services
      • THOP – TB, HIV and opportunistic diseases and pathogens
      • VBD – Vector borne diseases and pathogens
      • IHC – Individual health care
    • Research in numbers
      • 2020
      • 2019
      • 2018
      • 2017
    • Projects
      • Ongoing Projects
    • Members
      • Population health, policies and services
        • PPS PhD members
        • PPS non PhD members
      • TB, HIV and opportunistic diseases and pathogens
        • THOP PhD members
        • THOP non PhD members
      • Vector-borne diseases and pathogens
        • VBD PhD members
        • VBD non PhD members
      • Individual Health Care
        • IHC PhD members
        • IHC non PhD members
      • Technical / administrative support
  • Publications
  • Education
    • Master Theses
    • PhD Theses
  • Services
Home / Publicações / Contribution of efflux to the emergence of isoniazid and multidrug resistance in Mycobacterium tuberculosis.

Contribution of efflux to the emergence of isoniazid and multidrug resistance in Mycobacterium tuberculosis.

  • Autores: Amaral L, Baptista P, Couto I, Machado D, Perdigão J, Portugal I, Rodrigues L, Veigas B, Viveiros M
  • Journal: PLoS One
  • Link: http://www.ncbi.nlm.nih.gov/pubmed/?term=Contribution+of+Efflux+to+the+Emergence+of+Isoniazid+and+Multidrug+Resistance+in+Mycobacterium+tuberculosis

Multidrug resistant (MDR) tuberculosis is caused by Mycobacterium tuberculosis resistant to isoniazid and rifampicin, the two most effective drugs used in tuberculosis therapy. Here, we investigated the mechanism by which resistance towards isoniazid develops and how overexpression of efflux pumps favors accumulation of mutations in isoniazid targets, thus establishing a MDR phenotype. The study was based on the in vitro induction of an isoniazid resistant phenotype by prolonged serial exposure of M. tuberculosis strains to the critical concentration of isoniazid employed for determination of drug susceptibility testing in clinical isolates. Results show that susceptible and rifampicin monoresistant strains exposed to this concentration become resistant to isoniazid after three weeks; and that resistance observed for the majority of these strains could be reduced by means of efflux pumps inhibitors. RT-qPCR assessment of efflux pump genes expression showed overexpression of all tested genes. Enhanced real-time efflux of ethidium bromide, a common efflux pump substrate, was also observed, showing a clear relation between overexpression of the genes and increased efflux pump function. Further exposure to isoniazid resulted in the selection and stabilization of spontaneous mutations and deletions in the katG gene along with sustained increased efflux activity. Together, results demonstrate the relevance of efflux pumps as one of the factors of isoniazid resistance in M. tuberculosis. These results support the hypothesis that activity of efflux pumps allows the maintenance of an isoniazid resistant population in a sub-optimally treated patient from which isoniazid genetically resistant mutants emerge. Therefore, the use of inhibitors of efflux should be considered in the development of new therapeutic strategies for preventing the emergence of MDR-TB during treatment.

Share this:

  • Click to share on Facebook (Opens in new window)
  • Click to share on Twitter (Opens in new window)
  • Click to share on LinkedIn (Opens in new window)
  • Click to share on Pinterest (Opens in new window)
  • Click to share on WhatsApp (Opens in new window)
  • Click to print (Opens in new window)

Events

NOVA Sciencepreneur program: registration is open

  The Sciencepreneur ® program is aimed at NOVA scientists who are seeking to create value … [Read More...]

IHMT selected for the pilot phase of the Research Data Repository Service of the FCT

  In order to promote good practices in Open Science with regard to research data and … [Read More...]

Paulo Ferrinho interviewed for the new e-magazine of European and Developing Countries Clinical Trials Partnership (EDCTP)

Paulo Ferrinho, professor and Diretor of Public Global Health Departament at the Instituto de … [Read More...]

How can we improve the environmental performance of our laboratories?

  Every day in NOVA's laboratories research is carried out with the consumption of numerous … [Read More...]

Call for PhD Studentships

The Institute of Hygiene and Tropical Medicine (IHMT), Universidade Nova de Lisboa (NOVA), through … [Read More...]

IHMT | GHTM – APPLICATIONS ARE OPEN!

IHMT | GHTM - Applications are open for three research vacancies:   One position - PhD … [Read More...]

About GHTM

GHTM is a R&D Center that brings together researchers from IHMT with a track record in Tropical Medicine and International/Global Health. It aims at strengthening Portugal's role as a leading partner in the development and implementation of a global health research agenda. Our evidence-based interventions contribute to the promotion of equity in health and to improve the health of populations.

Contacts

Rua da Junqueira, 100
1349-008 Lisboa
Portugal
+351 213 652 600
+351 213 632 105

  • Facebook
  • YouTube

Subscribe Newsletter

  • How to get to GHTM/IHMT
  • GHTM Sessions
  • Research Groups
  • Cross-cutting issues
© Copyright 2023 IHMT-UNL Todos os Direitos Reservados.
  • Universidade Nova de Lisboa
  • Fundação para a Ciência e a Tecnologia

    Project UID/Multi/04413/2013