Decoding Multidrug Resistance Mechanism in Fusarium graminearum: Reduced Intracellular Drug Accumulation

Fusarium head blight (FHB), caused by Fusarium graminearum, is a major global threat to wheat production and food safety. Fungicides are the primary FHB control method, and prolonged single use accelerates resistance development. Sensitivity assays of 114 field isolates from four Chinese provinces to metconazole revealed EC₅₀ values ranging from 0.0082 to 0.2358 mg/L (mean 0.076 ± 0.049 mg/L). A stably resistant mutant (FY57-R1) was screened by UV mutagenesis, with a resistance factor of 71.34. FY57-R1 exhibited cross-resistance to prothioconazole, tebuconazole, phenamacril, pydiflumetofen, and azoxystrobin. FY57-R1 showed reduced vegetative growth but increased conidia production and enhanced tolerance to low-temperature, cell wall, and cell membrane stresses. No mutations or expression changes were detected in CYP51 genes, suggesting nontarget-site resistance. The intracellular fungicide accumulation was reduced in FY57-R1, suggesting the resistance mechanism might involve drug uptake or efflux. These findings elucidated multidrug resistance mechanisms, emphasizing the urgency of monitoring resistance and guiding sustainable FHB management.