Verapamil Modulates Activity of Antimicrobials Against Rapidly Growing Mycobacteria

Rapidly growing mycobacteria (RGM) have been causing diseases with an increasing incidence that require long and difficult treatment. In this regard, it is a priority to seek rapid and low-cost optimization of therapeutic alternatives. Thus, our objective is to explore the combined activity between verapamil (VP) and the antimicrobials clarithromycin, amikacin, and clofazimine (CFZ) against Mycobacterium smegmatis, Mycobacterium abscessus subsp. abscessus, Mycobacterium abscessus subsp. massiliense, Mycobacterium abscessus subsp. bolletii, Mycobacterium chelonae, and Mycobacterium fortuitum. According to the checkerboard assay, it was observed that the best combination was between VP and CFZ, with synergistic activity on all tested bacteria. The time-killing assay demonstrated that VP improved the killing of CFZ and extended its inhibitory activity 16 times. In this sense, VP has modulating activity with most of the tested antimicrobials, especially with CFZ, and thus may have potential activity in preventing bacterial resistance that could be pointed out as a model for synergism in attempts at screening molecules for RGM infection treatments.