Triazole resistance in Aspergillus fumigatus exposed to new chiral fungicide mefentrifluconazole.

Abstract

Triazole resistance in the human fungal pathogen Aspergillus fumigatus has been a growing challenge in clinic treatment with triazole drugs such as itraconazole. The fast evolvement of triazole resistance in A.fumigatus in the ecosystem has drawn great attention, and there has been a possible link between the application of triazole fungicides in agriculture and triazole resistance in A.fumigatus. The change in susceptibility of A.fumigatus exposed to the new chiral triazole fungicide mefentrifluconazole was investigated in this study. The results indicated that triazole resistance in A.fumigatus was acquired with exposure to mefentrifluconazole at a level of greater than or equal to 2mg L-1 in liquid medium and soil (not at 0.4 nor 1mg L-1 ). Interestingly, stereoselectivity was found in the acquisition of triazole resistance in A.fumigatus when exposed to mefentrifluconazole. R-mefentrifluconazole, which is very active on plant pathogens, exhibited stronger possibility in the development of the resistance in A.fumigatus than its antipode. Overexpression of cyp51A, AtrF, AfuMDR1 and AfuMDR4 were associated with the acquired resistance in A.fumigatus with hereditary stability. The results suggest that triazole resistance in A.fumigatus could be resulted from the selection of mefentrifluconazole at concentrations larger than 2mg L-1 . Mefentrifluconazole should be applied within the dosage recommended by good agricultural practice to avoid the resistance in A.fumigatus in soil. This also may be applicable to other triazole fungicides. © 2022 Society of Chemical Industry.