Cytochrome b5-Like Protein VdPBP1 Mediates Electron Transfer in Ergosterol Pathway to Confer Terbinafine Resistance of <i>Verticillium dahliae</i>

Fungal ergosterol biosynthesis relies on electron carriers to activate substrates, and thus, they are recognized as targets for fungicides. In this study, we demonstrated that a cytoplasm-localized cytochrome b5-like progesterone binding protein, VdPBP1, participated in vegetative growth, virulence, and metabolism of membrane components in <i>Verticillium dahliae</i>, especially ergosterol biosynthesis. As a stress sensor, its protein level was dose-dependently inhibited by terbinafine. VdPBP1 directly interacted with squalene epoxidase VdERG1 on the lipid droplets. Supplementing hemin and enhancing cytochrome P450 reductase system partly restored ergosterol metabolism and susceptibility phenotypes of <i>VdPBP1</i> mutants suggesting that electron input of VdPBP1 is crucial for maintaining VdERG1 expression and terbinafine tolerance. Structurally, terbinafine was immersed in VdPBP1's heme-binding region, which was essential for electron transfer rather than VdPBP1/VdERG1 interaction. These results not only revealed a new adaptor of ergosterol biosynthesis and drug resistance in <i>V. dahliae</i> but also provide a feasible control strategy for cotton Verticillium wilt.