Uncoupler SYP-14288 inducing multidrug resistance of Phytophthora capsici through overexpression of cytochrome P450 monooxygenases and P-glycoprotein

BACKGROUND Fungicide resistance has become a serious problem for different mode of action groups except for uncouplers, which makes their resistance mechanism a hot topic, which until now, has not been well clarified. SYP-14288, a newly developed diarylamine fungicide modeled on fluazinam, has shown good toxicity to both oomycete and fungus by the action of uncoupling. In this research, the resistance of Phytophthora capsici to SYP-14288 was studied to clarify the resistance mechanism of uncouplers. RESULTS The toxicity tests of resistant strains against SYP-14288 showed multidrug resistance. The high-performance liquid chromatography (HPLC) results showed that resistant strains could efflux the fungicide, and this ability could be inhibited by the efflux pump inhibitor amitriptyline. The target protein of amitriptyline is P-glycoprotein (P-gp), which was overexpressed in resistant strains. Three products of nitrate reduction of SYP-14288 were detected and determined by HPLC-Q-TOF. Eight cytochrome P450 monooxygenase (P450) proteins were differentially involved in the reduction reaction. CONCLUSION Both fungicide efflux and detoxification metabolism were involved in the resistance mechanisms of P. capsici to SYP-14288. © 2022 Society of Chemical Industry.