Tetrahydropyridine derivative as efflux inhibitor in Mycobacterium abscessus

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 Mycobacterium 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 NUNL02 showed activity against M. abscessus ; the MIC of AMI against ATCC 19997 was reduced by more than 16-fold, and the MIC of CIP against AT 52 was reduced by 4-fold. When combined with CLA, the MIC was reduced against all strains tested. In addition, to detect and quantify the activity of the efflux mechanism, we evaluated the intracellular accumulation kinetics of the fluorometric substrate ethidium bromide in the presence and absence of VP and NUNL02. NUNL02 was found to be a more effective efflux inhibitor than VP, which is the classical inhibitor. Conclusions Therefore, NUNL02 is a promising adjuvant in the treatment of infections caused by M. abscessus .