| Summary: | The basis of drug resistance in <i>Mycobacterium abscessus</i> is still poorly understood. Nevertheless, as seen in other microorganisms, the efflux of antimicrobials may also play a role in <i>M. abscessus</i> drug resistance. Here, we investigated the role of efflux pumps in clarithromycin resistance using nine clinical isolates of <i>M. abscessus</i> complex belonging to the T28 <i>erm</i>(41) sequevar responsible for the inducible resistance to clarithromycin. The strains were characterized by drug susceptibility testing in the presence/absence of the efflux inhibitor verapamil and by genetic analysis of drug-resistance-associated genes. Efflux activity was quantified by real-time fluorometry. Efflux pump gene expression was studied by RT-qPCR upon exposure to clarithromycin. Verapamil increased the susceptibility to clarithromycin from 4- to ≥64-fold. The efflux pump genes <i>MAB_3142</i> and <i>MAB_1409</i> were found consistently overexpressed. The results obtained demonstrate that the T28 <i>erm</i>(41) polymorphism is not the sole cause of the inducible clarithromycin resistance in <i>M.</i> <i>abscessus</i> subsp. <i>abscessus</i> or <i>bolletii</i> with efflux activity providing a strong contribution to clarithromycin resistance. These data highlight the need for further studies on <i>M. abscessus</i> efflux response to antimicrobial stress in order to implement more effective therapeutic regimens and guidance in the development of new drugs against these bacteria.
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