The MBF complex orchestrates BbOSD-mediated lipid metabolism, development, oxidative stress, and pathogenic virulence...

This study establishes the MBF transcription complex (BbSwi6/BbMbp1) as a central regulator of lipid metabolism and virulence in Beauveria bassiana by directly controlling the short-chain dehydrogenase/reductase (SDR) gene BbOSD. Deletion of BbSWI6, BbMBP1 and BbOSD caused severe lipid dysregulation, including a significant reduction in mycelial lipids and, critically, failure to deplete host lipids during Galleria mellonella infection. This impaired host lipid assimilation underlies the mutants' attenuated virulence. BbOSD expression was drastically downregulated in MBF mutants and required for wild-type levels of dramatic induction (∼10-fold) when lipids served as the sole carbon source. Yeast one-hybrid confirmed BbMbp1 binding to the BbOSD promoter, establishing MBF-mediated metabolic reprogramming towards lipid catabolism during nutrient stress. BbOsd, structurally confirmed as an SDR, dynamically localized to lipid droplets during exogenous lipid utilization. BbOSD deletion severely impaired asexual reproduction, with conidiation and blastospore production reductions exacerbated under lipid-rich conditions. The ΔBbosd mutant also exhibited heightened sensitivity to oxidative stress and catastrophically diminished blastospore yield under oxidative challenge. Consequently, virulence was significantly attenuated via different infection routes. Collectively, the MBF-BbOSD axis integrates lipid homeostasis, development, and oxidative defense. Disruption simultaneously compromises these functions, directly diminishing virulence. This work fundamentally expands the conserved MBF complex's role beyond cell cycle regulation, positioning efficient lipid metabolism orchestrated by MBF-BbOSD as a cornerstone of entomopathogenicity.