Is the efflux pump inhibitor Verapamil a potential booster for isoniazid against Mycobacterium tuberculosis?

Authors

  • Renata Claro Ribeiro do Amaral State University of Maringa, Postgraduation in Bioscience and Physiopathology
  • Katiany Rizzieri Caleffi-Ferracioli State University of Maringa, Postgraduation in Bioscience and Physiopathology
  • Fernanda de Oliveira Demitto State University of Maringa, Postgraduation in Health Sciences
  • Aryadne Larissa de Almeida State University of Maringa, Postgraduation in Bioscience and Physiopathology
  • Vera Lucia Dias Siqueira State University of Maringa, Postgraduation in Bioscience and Physiopathology
  • Regiane Bertin de Lima Scodro State University of Maringa, Postgraduation in Health Sciences
  • Clarice Queico Fujimura Leite Paulista State University, School of Pharmaceutical Science, Laboratory of Mycobacteriology “Prof. Dr. Hugo David”
  • Fernando Rogério Pavan Paulista State University, School of Pharmaceutical Science, Laboratory of Mycobacteriology “Prof. Dr. Hugo David”
  • Rosilene Fressatti Cardoso State University of Maringa, Postgraduation in Bioscience and Physiopathology https://orcid.org/0000-0001-6228-4780

DOI:

https://doi.org/10.1590/s2175-97902020000218309

Keywords:

Tuberculosis, Multidrug-resistance, Efflux pumps, Efflux pumps inhibitors, Isoniazid

Abstract

The membrane-based efflux pump systems are recognized to have an important role in pathogenicity and drug resistance in Mycobacterium tuberculosis by the extrusion of toxic substrates and drugs from the inner bacillus. This study aimed to investigate the in vitro interaction of Verapamil (VP), an efflux pump inhibitor, with the classical first-line anti-tuberculosis drug isoniazid (INH) in resistant and susceptible M. tuberculosis clinical isolates. Seven multidrug-resistant (MDR), three INH monoresistant and four susceptible M. tuberculosis clinical isolates were tested for the INH and VP combination by modified Resazurin Microtiter Assay Plate (REMA). Fractional Inhibitory Concentration (FIC) and Modulation Factor (MF) were determined. The INH plus VP combination showed no significant change in the Minimum inhibitory concentration (MIC) values of INH (FIC≥ 0.5; MF=1 or 2).The use of VP in tuberculosis therapy should be managed carefully, considering the resistance caused by specific mutation in katG and inhA genes, in which the use of these EPIs may have no success. The use of EPIs as an adjunctive drug in the anti-tuberculosis therapy should be further investigated on a larger number of M. tuberculosis clinical isolates with different resistant profile.

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Published

2020-12-09

How to Cite

Amaral, R. C. R. do ., Caleffi-Ferracioli, K. R. ., Demitto, F. de O. ., Almeida, A. L. de ., Siqueira, V. L. D. ., Scodro, R. B. de L. ., Leite, C. Q. F. ., Pavan, F. R. ., & Cardoso, R. F. . (2020). Is the efflux pump inhibitor Verapamil a potential booster for isoniazid against Mycobacterium tuberculosis?. Brazilian Journal of Pharmaceutical Sciences, 56, e18309 . https://doi.org/10.1590/s2175-97902020000218309

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