6-methylflavone exerts selective antimycobacterial activity with membrane energetics disruption and demonstrates therapeutic potential against Mycobacterium abscessus infection

Despite the increasing global incidence of nontuberculous mycobacterial (NTM) diseases, effective treatment regimens remain limited. In particular, Mycobacterium abscessus exhibits notoriously multidrug resistance, making its treatment extremely challenging. In this study, we identified 6-methylflavone (6-MF) as a selective antimycobacterial compound through screening of synthetic flavonoid library. 6-MF specifically inhibited mycobacterial growth and disrupted membrane energetics while showing negligible effects on other bacterial genera. Mycobacteria have unique energy metabolic systems distinct to other bacteria and have been reported to be particularly susceptible to energy metabolism disruptors, such as bedaquiline, clofazimine, and telacebec (Q203). We hope this research will inspire further studies aimed at developing novel antimycobacterial strategies based on energetics disruption.