In Vitro Antibacterial Activity of Myxin Against Mycobacterium abscessus

Nontuberculous mycobacteria (NTM) infections, especially those caused by Mycobacterium abscessus, are extremely difficult to treat due to the organisms' intrinsic resistance to many antimicrobials. Myxin is a naturally occurring phenazine-5,10-dioxide antibiotic from Sorangium sp., notable for its broad-spectrum antimicrobial activity. In this study, we determined the susceptibilities of Myxin against 11 NTM reference strains and 194 clinical M. abscessus isolates using microdilution assays. Additionally, time-kill kinetic experiments were performed to distinguish the clearing efficiency of Myxin in broth. We also evaluated the efficacy of Myxin against intracellular M. abscessus in THP-1 macrophages. Checkerboard assays assessed the interactions between Myxin and eight clinically important anti-NTM antibiotics. Myxin demonstrated potent activity against M. abscessus with low MIC values (MIC₅₀ = 0.125 mg/L and MIC₉₀ = 0.5 mg/L). Treatment with 20 × MIC of Myxin in 7H9 broth resulted in up to 10 log₁₀ CFU/mL reduction after 4 days of incubation. An intracellular concentration-dependent bactericidal effect of Myxin was observed in THP-1 macrophages. Myxin exhibited no antagonism in combination with standard anti-NTM drugs. As such, Myxin represents a promising candidate for the treatment of M. abscessus and other NTM infections.