Resistance Risk Assessment for the New OSBP Inhibitor Y18501 in Pseudoperonospora cubensis and Point Mutations (G705V, L798W, and I812F) in PscORP1 that Confer Resistance

Y18501 is a new oxysterol-binding protein inhibitor (OSBPI) that shows strong inhibitory activity against Pseudoperonospora cubensis. In this study, the sensitivities of 159 Ps. cubensis isolates to Y18501 were determined, with EC50 values ranging from 0.001 to 11.785 mu g/mL, indicating that a Y18501-resistant subpopulation has appeared in the field. Ten Y18501-resistant mutants were obtained by fungicide adaptation and displayed fitness equal to or stronger than their parental isolates, which suggests that the resistance risk of Ps. cubensis to Y18501 is high. The consecutive applications of Y18501 in the field resulted in the rapid resistance of Ps. cubensis and decreased control efficacy of cucumber downy mildew (CDM), which could be alleviated by compounding with mancozeb. A positive cross-resistance was detected between Y18501 and oxathiapiprolin. The amino acid substitutions G705V, L798W, and I812F in PscORP1 conferred resistance to Y18501 in Ps. cubensis, which was validated by molecular docking and molecular dynamics simulations.

Automated summary

Y18501 is found to be a potent inhibitor against Pseudoperonospora cubensis and a resistant subpopulation of Ps. cubensis to Y18501 has emerged in the field. The consecutive applications of Y18501 in the field have led to the rapid resistance of Ps. cubensis and decreased control efficacy of cucumber downy mildew, which can be alleviated by compounding with mancozeb. A positive cross-resistance is detected between Y18501 and oxathiapiprolin, and specific amino acid substitutions in PscORP1 confer resistance to Y18501 in Ps. cubensis.