Identification of Novel Mutations Associated with Bedaquiline Resistance in Mycobacterium Marinum

Objective: Because infections caused by nontuberculous mycobacteria (NTM) are rapidly increasing globally, a need exists for developing novel antibiotics and discovering the mechanism of resistance. This research was aimed at understanding bedaquiline resistance in model NTM species Mycobacterium marinum ( M. ). Methods: The M strain subjected to mutant selection with different concentrations BDQ. After three rounds evolution, 58 BDQ-resistant mutants were isolated WGS. results confirmed through PCR Sanger sequencing. Results: We identified seven genetic mutations among these mutants. highest drug (6–10× MIC) associated mutation AtpB, primary biochemical target BDQ Mtb. Numerous insertions mapped gene MMAR_1007 (46/58), which encodes homolog Rv0678 (MmpR) More than 93% (54/58) contained single (G563A) MMAR_4049 , integral membrane protein YrbE3A-1. Conclusion: Both target-based efflux-based actions contribute marinum. Our findings may aid potent anti-NTM (BDQ-based) regimens diagnostic assays detection .