Bixafen, a succinate dehydrogenase inhibitor fungicide, causes microcephaly and motor neuron axon defects during development

New fungicides are tools to manage fungal diseases and overcome emerging resistance in fugnal pathogens. In this study, a total of 121 isolates of Fusarium fujikuroi, the causal agent of rice bakanae disease (RBD), were collected from various geographical regions of China, and their sensitivity to a novel succinate dehydrogenase inhibitor (SDHI)fungicide ‘pydiflumetofen’ was evaluated. The 50% effective concentration (EC50) value of pydiﬂumetofen for mycelial growth suppression ranged from 0.0101 to 0.1012 μg/ml and for conidial germination inhibition ranged from 0.0051to 0.1082 μg/ml. Pydiﬂumetofen treated hyphae showed contortion and increased branching, cell membrane permeability, and glycerol content significantly. The result of electron microscope transmission indicated that pydiﬂumetofen damaged the mycelial cell wall and the cell membrane, and almost broken up the cells, which increased the intracellular plasma leakage. There was no cross-resistance between pydiflumetofen and the widely used fungicides such as carbendazim, prochloraz, and phenamacril. Pydiflumetofen was found safe to seeds and rice seedlings of four rice cultivars, used up to 400 μg/ml. Seed treatment significantly decreased the rate of diseased plants in the greenhouse as well as in field trials in 2017 and 2018. Pydiflumetofen showed superb results against RBD, when used at 10 or 20 g a.i./100 kg of treated seeds, providing over 90% control efficacy (the highest control efficacy was up to 97%), which was significantly higher than that of 25% phenamacril (SC) at 10g or carbendazim at 100 g. Pydiflumetofen is highly effective against F. fujikuroi growth and sporulation as well as RBD in the field.

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Bixafen, a succinate dehydrogenase inhibitor fungicide, causes microcephaly and motor neuron axon defects during development

10.1101/2020.08.15.252254 ◽

2020 ◽

Author(s):

Alexandre Brenet ◽

Rahma Hassan-Abdi ◽

Nadia Soussi-Yanicostas

Keyword(s):

Motor Neuron ◽

Succinate Dehydrogenase ◽

Toxicity Testing ◽

Mitochondrial Respiratory Chain ◽

Modern Agriculture ◽

Transgenic Lines ◽

Vertebrate Model ◽

The Central Nervous System

AbstractSuccinate dehydrogenase inhibitors (SDHIs), the most widely used fungicides in agriculture today, act by blocking succinate dehydrogenase (SDH), an essential and evolutionarily conserved component of mitochondrial respiratory chain. Recent results showed that several SDHIs used as fungicides not only inhibit the SDH activity of target fungi but also block this activity in human cells in in vitro models, revealing a lack of specificity and thus a possible health risk for exposed organisms, including humans. Despite the frequent detection of SDHIs in the environment and on harvested products and their increasing use in modern agriculture, their potential toxic effects in vivo, especially on neurodevelopment, are still under-evaluated. Here we assessed the neurotoxicity of bixafen, one of the latest-generation SDHIs, which had never been tested during neurodevelopment. For this purpose, we used a well-known vertebrate model for toxicity testing, namely zebrafish transparent embryos, and live imaging using transgenic lines labelling the brain and spinal cord. Here we show that bixafen causes microcephaly and defects on motor neuron axon outgrowth and their branching during development. Our findings show that the central nervous system is highly sensitive to bixafen, thus demonstrating in vivo that bixafen is neurotoxic in vertebrates and causes neurodevelopmental defects. This work adds to our knowledge of the toxic effect of SDHIs on neurodevelopment and may help us take appropriate precautions to ensure protection against the neurotoxicity of these substances.

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Succinate dehydrogenase inhibitor (SDHI) fungicide resistance prevention strategy

New Zealand Plant Protection ◽

10.30843/nzpp.2011.64.5972 ◽

2011 ◽

Vol 64 ◽

pp. 119-124 ◽

Cited By ~ 4

Author(s):

A.H. McKay ◽

G.C. Hagerty ◽

G.B. Follas ◽

M.S. Moore ◽

M.S. Christie ◽

...

Keyword(s):

New Zealand ◽

High Risk ◽

Succinate Dehydrogenase ◽

Fungicide Resistance ◽

Fungal Pathogens ◽

Resistance Management ◽

Resistance Development ◽

Development Of Resistance ◽

Action Committee ◽

Succinate Dehydrogenase Inhibitor

Succinate dehydrogenase inhibitor (SDHI) fungicides are currently represented in New Zealand by eight active ingredients bixafen boscalid carboxin fluaxapyroxad fluopyram isopyrazam penthiopyrad and sedaxane They are either currently registered or undergoing development in New Zealand for use against a range of ascomycete and basiodiomycete pathogens in crops including cereals ryegrass seed apples pears grapes stonefruit cucurbits and kiwifruit These fungicides are considered to have medium to high risk of resistance development and resistance management is recommended by the Fungicide Resistance Action Committee (FRAC) in Europe Guidelines are presented for use of SDHI fungicides in New Zealand to help avoid or delay the development of resistance in the fungal pathogens that they target

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Fusarium graminearum FgSdhC1 point mutation A78V confers resistance to the succinate dehydrogenase inhibitor pydiflumetofen

Pest Management Science ◽

10.1002/ps.6795 ◽

2022 ◽

Author(s):

Wenyong Shao ◽

Jingrui Wang ◽

Huiyuan Wang ◽

Ziyue Wen ◽

Chao Liu ◽

...

Keyword(s):

Succinate Dehydrogenase ◽

Point Mutation ◽

Fusarium Graminearum ◽

Succinate Dehydrogenase Inhibitor

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Resistance risk assessment for a novel succinate dehydrogenase inhibitor pydiflumetofen in Fusarium asiaticum

Pest Management Science ◽

10.1002/ps.6053 ◽

2020 ◽

Vol 77 (1) ◽

pp. 538-547

Author(s):

Wenchan Chen ◽

Lingling Wei ◽

Weicheng Zhao ◽

Bingran Wang ◽

Huanhuan Zheng ◽

...

Keyword(s):

Risk Assessment ◽

Succinate Dehydrogenase ◽

Resistance Risk ◽

Fusarium Asiaticum ◽

Succinate Dehydrogenase Inhibitor

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NMDA Receptor Involvement in Toxicity to Dopamine Neurons In Vitro Caused by the Succinate Dehydrogenase Inhibitor 3-Nitropropionic Acid

Journal of Neurochemistry ◽

10.1046/j.1471-4159.1995.64010455.x ◽

2002 ◽

Vol 64 (1) ◽

pp. 455-458 ◽

Cited By ~ 53

Author(s):

Gail D. Zeevalk ◽

Ethel Derr-Yellin ◽

William J. Nicklas

Keyword(s):

Nmda Receptor ◽

Succinate Dehydrogenase ◽

Dopamine Neurons ◽

Nitropropionic Acid ◽

Succinate Dehydrogenase Inhibitor ◽

3 Nitropropionic Acid

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Characterization of the Excitotoxic Potential of the Reversible Succinate Dehydrogenase Inhibitor Malonate

Journal of Neurochemistry ◽

10.1046/j.1471-4159.1995.64010430.x ◽

2002 ◽

Vol 64 (1) ◽

pp. 430-436 ◽

Cited By ~ 80

Author(s):

James G. Greene ◽

J. Timothy Greenamyre

Keyword(s):

Succinate Dehydrogenase ◽

Succinate Dehydrogenase Inhibitor

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Sensitivity of Alternaria alternata from Citrus to Boscalid and Polymorphism in Iron-Sulfur and in Anchored Membrane Subunits of Succinate Dehydrogenase

Plant Disease ◽

10.1094/pdis-04-14-0374-re ◽

2015 ◽

Vol 99 (2) ◽

pp. 231-239 ◽

Cited By ~ 5

Author(s):

Byron Vega ◽

Megan M. Dewdney

Keyword(s):

Succinate Dehydrogenase ◽

Alternaria Alternata ◽

Mycelial Growth ◽

Conidial Germination ◽

Brown Spot ◽

Sequence Comparisons ◽

Sensitivity Tests ◽

Alternaria Brown Spot ◽

Succinate Dehydrogenase Inhibitor

Boscalid, a succinate dehydrogenase inhibitor (SDHI), was registered in 2011 to control Alternaria brown spot (ABS) of citrus, caused by Alternaria alternata. In this study, the effect of boscalid on mycelial growth, conidial germination, and resazurin reduction was established in a subset of 16 sensitive isolates using three different media. Conidial germination and mycelial growth inhibition were not suppressed even at higher concentrations of boscalid, although effective concentration to inhibit 50% growth (EC50) values were established with each method. Resazurin reduction produced the lowest EC50 values and was selected for further sensitivity tests. In total, 419 isolates, never exposed to boscalid and collected from Florida tangerine orchards between 1996 to 2012, were tested for boscalid sensitivity. The sensitivity distribution was a unimodal curve with a mean EC50 value of 0.60 μg/ml and a range of 0.07 to 5.84 μg/ml. The molecular characterization of the succinate dehydrogenase (SDH) genes were also determined in a subset of 15 isolates, exhibiting great variability in boscalid sensitivity, by cloning and sequencing the sdhB, sdhC, and sdhD genes. Sequence comparisons of the SDH complex revealed the presence of mutations in 14 of 15 isolates. In total, 21 mutations were identified. Double and multiple mutations were observed in SDHC and SDHD, respectively. In SDHB, 4 mutations were observed while, in SDHC and SDHD, 5 and 12 mutations were detected, respectively. No mutations were found in the highly conserved histidine residues at positions 277 in SDHB, 134 in SDHC, and 133 in SDHD, typically observed in SDHI-resistant isolates. Our findings suggest that A. alternata populations from Florida are sensitive to boscalid and it could be used in ABS spray programs. Boscalid resistance is currently not a problem, although further monitoring for resistance is advisable.

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