In vitro activity of cinacalcet against Mycobacterium abscessus

Mycobacterium abscessus ( M. abscessus ) is a rapidly growing nontuberculous mycobacterium associated with persistent pulmonary infections and limited therapeutic options. In this study, we employed a high-throughput drug repurposing strategy to identify compounds with activity against M. abscessus and performed a systematic evaluation of the antibacterial properties of cinacalcet (CIN), including its activity against planktonic bacteria, biofilms and intracellular bacteria. CIN inhibited the growth of the reference strain ATCC 19,977, with a minimum inhibitory concentration (MIC) of 4 µg/mL and a minimum bactericidal concentration (MBC) of 32 µg/mL, indicating predominantly bacteriostatic activity. In contrast, reduced susceptibility was observed among clinical isolates, with MIC values ≥ 16 µg/mL. In macrophage infection models, CIN exhibited modest intracellular antibacterial activity, while cytotoxicity assays revealed a relatively narrow concentration range tolerated by host cells. Time-kill assays showed that CIN exerted a concentration-dependent inhibitory effect without sustained bactericidal activity. In addition, no synergistic interaction was observed between CIN and clinically relevant anti- M. abscessus antibiotics. CIN reduced biofilm formation in a concentration-dependent manner but showed limited activity against mature biofilms and biofilm-embedded bacteria. Overall, this study provides a comprehensive characterization of the antibacterial activity of CIN against M. abscessus and identifies CIN as a repurposed compound with previously unrecognized activity against M. abscessus , providing a starting point for future optimization and mechanistic investigation.