Triazole resistance in Aspergillus fumigatus exposed to new chiral fungicide mefentrifluconazole

Abstract

BACKGROUND 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. RESULTS The results indicated that triazole resistance in A. fumigatus was acquired with exposure to mefentrifluconazole at a level of greater than or equal to 2 mg L−1 in liquid medium and soil (not at 0.4 nor 1 mg 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. CONCLUSION The results suggest that triazole resistance in A. fumigatus could be resulted from the selection of mefentrifluconazole at concentrations larger than 2 mg 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.

Mefentrifluconazole-Resistant Risk and Resistance-Related Point Mutation in FpCYP51B of Fusarium pseudograminearum

“…The overexpression of CcCYP51A and CcCYP51B also was associated with mefentrifluconazole resistance in Corynespora cassiicola . Overexpression of cyp51A , AtrF , AfuMDR1 , and AfuMDR4 were associated with the acquired mefentrifluconazole resistance in Aspergillus fumigatus with hereditary stability . This investigation discovered the L144F substitution in FpCYP51B in four mutants that exhibited resistance to mefentrifluconazole.…”

Enantioselective Degradation and Bioactivity Mechanism of a New Chiral Fungicide Fluindapyr in Paddy Ecosystems

“…19 In the stereoselectivity of fungicide resistance, R-mefentrifluconazole exhibited stronger resistance in Aspergillus fumigatus. 20 On account of 17.73 times higher activity against Fusarium graminearum, R-(−)-prothioconazole induce F. graminearum into producing more DON. 21 In chiral amide fungicides, the enantioseparation mechanism of penflufen was explained by computational chemistry, 22 and S-penflufen was 54 times more toxic to Danio rerio and 148 times more toxic to R. solani.…”

“…In the stereoselectivity of fungicide resistance, R -mefentrifluconazole exhibited stronger resistance in Aspergillus fumigatus . On account of 17.73 times higher activity against Fusarium graminearum, R -(−)-prothioconazole induce F. graminearum into producing more DON .…”

Multiomics Sequencing and AlphaFold2 Analysis of the Stereoselective Behavior of Mefentrifluconazole for Bioactivity Improvement and Risk Reduction

“…Triazole fungicides occupy a significant position in the global fungicide market. , Triazole fungicides have excellent antifungal activity and can effectively control powdery mildew, rust, sheath blight, and leaf spot . Mefentrifluconazole is a new-generation triazole fungicide developed by BASF . Mefentrifluconazole has a unique isopropyl alcohol structure that effectively solves the problem of resistance to triazole fungicides .…”

“…Mefentrifluconazole has a unique isopropyl alcohol structure that effectively solves the problem of resistance to triazole fungicides . Studies have shown that mefentrifluconazole has excellent bioactivity against powdery mildew, leaf blight, sheath blight, and rice blast. , Currently, mefentrifluconazole is registered under the name Revysol in more and more countries and has broad application prospects.…”