BEM2, a RHO GTPase Activating Protein That Regulates Morphogenesis in S. cerevisiae, Is a Downstream Effector of Fungicidal Action of Fludioxonil

Fludioxonil belongs to the phenylpyrrole group of fungicides with a broad antifungal spectrum that has been widely used in agricultural practices for the past thirty years. Although fludioxonil is known to exert its fungicidal action through group III hybrid histidine kinases, the downstream effector of its cytotoxicity is poorly understood. In this study, we utilized a S. cerevisiae model to decipher the cytotoxic effect of fludioxonil. Through genome wide transposon mutagenesis, we have identified Bem2, a Rho GTPase activating protein, which is involved in this process. The deletion of BEM2 resulted in fludioxonil resistance. Our results showed that both the GAP and morphogenesis checkpoint activities of Bem2 were important for this. We also provided the genetic evidence that the role of Bem2 in the cell wall integrity (CWI) pathway and cell cycle regulation could contribute to the fludioxonil resistance phenotype.