Tetrahydropyridine derivative as efflux inhibitor in Mycobacterium abscessus

Júlia S. Vianna, Ivy B. Ramis, Dienefer Bierhals, Andrea von Groll, Daniela F. Ramos, Nilo Zanatta, Maria Cristina Lourenço, Miguel Viveiros, Pedro E. Almeida da Silva

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Objectives: This study aimed to evaluate a tetrahydropyridine derivative (THP) as a potential inhibitor of the efflux mechanism and modulator of the high level of antimicrobial resistance usually observed in members of the Mycobacterium abscessus (M. abscessus) group. Methods: The strain M. abscessus subsp. abscessus (ATCC 19997) was used as reference, in addition to three clinical isolates: M. abscessus subsp. abscessus (AT 07), and two M. abscessus subsp. bolletii (AT 46 and AT 52). The minimum inhibitory concentration (MIC) of amikacin (AMI), ciprofloxacin (CIP), clarithromycin (CLA), verapamil (VP), and THP derivative (NUNL02) was determined. Results: The NUNL02 showed activity against M. abscessus; the MIC of AMI against ATCC 19997 was reduced more than 16-fold, and the MIC of CIP against AT 52 was reduced four-fold. When combined with CLA, the MIC was reduced against all tested strains. In addition, to detect and quantify the activity of the efflux mechanism, the intracellular accumulation kinetics of the fluorometric substrate ethidium bromide in the presence and absence of VP and NUNL02 were evaluated. The NUNL02 was found to be a more effective efflux inhibitor than VP, which is the classical inhibitor. Conclusions: The tetrahydropyridine derivative, NUNL02, is a promising adjuvant in the treatment of infections caused by M. abscessus.

Original languageEnglish
Pages (from-to)296-299
Number of pages4
JournalJournal of Global Antimicrobial Resistance
Volume17
DOIs
Publication statusPublished - 1 Jun 2019

Keywords

  • Efflux pump
  • Mycobacteria
  • Tetrahydropyridine

UN Sustainable Development Goals (SDGs)

  • SDG 3 - Good Health and Well-Being

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