Regulation of ABC Transporters and Ergosterol Biosynthesis by the Transcription Factor FvADS-1 Controls Azole Resistance and Virulence in Fusarium verticillioides

Fusarium verticillioides is a significant agricultural pathogen and an emerging causative agent of invasive fusariosis in clinical settings. Fusarium species frequently exhibit resistance to available antifungal agents, yet the molecular mechanisms underlying azole resistance remain poorly characterized. In this study, we identified the Zn(II)2Cys6 transcription factor FvADS-1 as a positive regulator of the azole stress response in F. verticillioides. The transcription of FvADS-1 was significantly induced by ketoconazole (KTC), and its deletion increased the susceptibility to multiple azole compounds. Mechanically, FvADS-1 positively regulates the KTC-induced expression of genes encoding ABC transporters and ergosterol biosynthesis enzymes, thereby modulating intracellular KTC accumulation and sterol homeostasis under azole stress. Furthermore, FvADS-1 positively regulates the transcriptional response of peroxisomal genes and contributes to fungal tolerance to oxidative stress. Notably, deletion of FvADS-1 attenuates the virulence of F. verticillioides on maize. Overall design: For F. verticillioides, 107 conidia were inoculated in YPD liquid medium and cultured at 28°C with shaking (200 rpm) for 20 h. Then the mycelia were treated with or without 2 µg/mL KTC for 16 h. After harvest, the mycelia were finely grounded into powder in liquid nitrogen. RNA was extracted according to standard TRIzol method (Invitrogen, Carlsbad, CA, United States) and followed by sample analysis. Transcriptomic profiles of the F. verticillioides wild-type and FvADS-1 deletion strains, either treated with or without KTC, were analyzed by high-throughput RNA sequencing (RNA-seq).