Multiple Mutations in SDHB and SDHC₂ Subunits Confer Resistance to the Succinate Dehydrogenase Inhibitor Cyclobutrifluram in Fusarium fujikuroi

Abstract

Fusarium fujikuroi is one of the dominant phytopathogenic fungi causing rice bakanae disease worldwide. Cyclobutrifluram is a novel succinate dehydrogenase inhibitor (SDHI), which shows strong inhibitory activity against F. fujikuroi. The baseline sensitivity of 112 F. fujikuroi to cyclobutrifluram was determinated with a mean EC50 value of 0.025 μg/mL. A total of 17 resistant mutants were obtained by fungicide adaptation and displayed equal or slightly weaker fitness than parental isolates, which suggests that the resistance risk of F. fujikuroi to cyclobutrifluram is medium. A positive cross-resistance was detected between cyclobutrifluram and fluopyram. The amino acid substitutions H248L/Y of FfSdhB and G80R or A83V of FfSdhC2 conferred cyclobutrifluram resistance in F. fujikuroi, which was validated by molecular docking and protoplast transformation. The results indicate that the affinity between cyclobutrifluram and FfSdhs obviously decreased after point mutations, causing the resistance of F. fujikuroi.

Study on Mechanisms of Resistance to SDHI Fungicide Pydiflumetofen in Fusarium fujikuroi

“…Mutations in the SDH subunit affect its enzymatic activity, which has been reported in different species. Boscalid-resistant mutant SsSdhB A11V of S. sclerotioru , Pyd-resistant mutants FaSdhB H248Y , FaSdhC 1 A64V , and FaSdhC 1 R67K of F. asiaticum, cyclobutrifluram-resistant mutants FfSdhB H248L/Y of F. fujikuroi all exhibited higher SDH activity than their wild-type parental strains. Similarly, the SDH enzyme activities of the 12 PydR mutants were significantly higher than those of their parental strains in this study.…”

“…Tricarboxylic acid (TCA) cycles and electron respiration chains are the main pathways of energy metabolism. The succinate dehydrogenase (SDH) complex is composed of four protein subunits (SdhA, SdhB, SdhC, and SdhD) involved in the regulation of the respiratory chain and TCA cycle. − The flavonoid proteins SdhA and iron–sulfur SdhB are exposed to the mitochondrial matrix, while two other hydrophobic proteins (SdhC and SdhD) bind to SdhAB dimers on the mitochondrial inner membrane to anchor complex II. − SDHI fungicides specifically interfere with respiration by blocking the SDH ubiquinone (UQ) binding site formed by the highly conserved SdhB, SdhC, and SdhD residues . Recently, amino acid alterations in SdhB, SdhC, and SdhD causing resistance to SDHI have been reported. ,− The Fungicide Resistance Action Committee (FRAC) considers SDHI at medium to high risk for resistance development () .…”

Synthetic Approaches to the 2019–2020 New Agrochemicals

“…6 It shows excellent control of several plant-parasitic nematodes, 67 but is also highly effective against soil-borne fungal diseases, for instance those caused by Fusarium pseudograminearum 68 and Fusarium fujikuroi. 69 Its cis-substituted cyclobutane ring is characterized by a predominant S,S-configuration. Cyclobutrifluram (55) can be seen as a conformationally locked analog of fluopyram ( 56), 70 which also has fungicidal and nematicidal activity (Figure 10).…”

Discovery of Novel Aminocyclobutanecarboxylic Acid Derivatives as Succinate Dehydrogenase Inhibitors

“…4,5 The control of phytopathogenic fungi mainly depends on the repeated use of chemical fungicides, which causes rapid development of resistance. 6 The resistance of triazoles and QoI inhibitors (strobilurins) seriously affects agricultural security. 7−9 To address these issues, the environmentally friendly and low toxic agricultural fungicides have become a crucial subject of research.…”

“…Fungi as a class of eukaryotic microorganisms extensively exist in natural environments . Phytopathogenic fungi have long been regarded as severe threat to crops, and their infections on crops are the most devastating diseases, which account for 16% of crop losses worldwide. , In addition to endangering food security, human and animal’s health, the development of phytopathogenic fungi in host plants have permanently disturbed the normal metabolic equilibrium inside living creatures. , The control of phytopathogenic fungi mainly depends on the repeated use of chemical fungicides, which causes rapid development of resistance . The resistance of triazoles and QoI inhibitors (strobilurins) seriously affects agricultural security. − To address these issues, the environmentally friendly and low toxic agricultural fungicides have become a crucial subject of research.…”