Antifungal activity of bamemacrolactine C against Talaromyces marneffei and its possible mechanisms of action.

This article focuses on the investigation of bamemacrolactine C (BAC), a novel 24-membered macrolide compound, for its antifungal activity and mechanism of action against the pathogenic fungus Talaromyces marneffei. BAC demonstrated concentration-dependent antifungal effects with a minimum inhibitory concentration (MIC) of 35.29 μg/ml and showed additive effects when combined with amphotericin B or fluconazole. Mechanistic studies revealed that BAC disrupts fungal cell membrane integrity, causing nucleic acid leakage and reducing activities of membrane-associated enzymes (Na+/K+-ATPase and Ca2+-ATPase), while also inhibiting intracellular enzymes involved in energy metabolism, including ATP, malate dehydrogenase, and succinate dehydrogenase. Proteomic analysis identified downregulation of ATP-citrate lyase (ACLY), a key enzyme in the tricarboxylic acid (TCA) cycle, as a potential molecular target, supported by molecular docking results indicating strong binding affinity. These findings suggest BAC's multifaceted antifungal mechanism involves both membrane disruption and interference with fungal energy metabolism, highlighting its potential as a novel therapeutic agent against T. marneffei infections.