Inhibition of acetyl-CoA carboxylase by spirotetramat causes lipid depletion and surface coat deficiency in nematodes

Abstract

Plant-parasitic nematodes pose a significant threat to agriculture causing annual yield losses worth more than 100 billion US$. Nematode control often involves the use of nematicides, but many of them including non-selective fumigants have been phased out, particularly due to ecotoxicological concerns. Thus new control strategies are urgently needed. Spirotetramat (SPT) is used as phloemmoble systemic insecticide targeting acetyl-CoA carboxylase (ACC) of pest insects and mites upon foliar application. Our studies revealed that SPT known to be activated in planta to SPT-enol acts as a developmental inhibitor of the free-living nematode Caenorhabditis elegans and the plant-parasitic nematode Heterodera schachtii. Exposure to SPT-enol leads to larval arrest and disruption of the life cycle. Furthermore, SPT-enol inhibits nematode ACC activity, affects storage lipids, fatty acid composition and disrupts surface coat synthesis. Silencing of H. schachtii ACC by RNAi induced similar phenotypes and thus mimics the effects of SPT-enol, supporting the conclusion that SPT-enol acts on nematodes by inhibiting ACC. Our studies demonstrated that the inhibition of de novo lipid biosynthesis by interfering with nematode ACC is a new nematicidal mode of action addressed by spirotetramat, a well-known systemic insecticide for sucking pest control.

New reduced-risk agricultural nematicides - rationale and review

“…To be active against nematodes, the compound needs to be hydrolyzed in the plant to the active spirotetramat-enol form ( Vang et al, 2016 ). In C. elegans , spirotetramat-enol leads to arrested larval development and disruption of the life cycle ( Vang et al, 2016 ; Gutbrod et al, 2018 ). The nematicide also inhibits acetyl-CoA carboxylase activity, storage of lipids, fatty acid composition, and disruption of surface coat synthesis in C. elegans ( Gutbrod et al, 2018 ).…”

“…In C. elegans , spirotetramat-enol leads to arrested larval development and disruption of the life cycle ( Vang et al, 2016 ; Gutbrod et al, 2018 ). The nematicide also inhibits acetyl-CoA carboxylase activity, storage of lipids, fatty acid composition, and disruption of surface coat synthesis in C. elegans ( Gutbrod et al, 2018 ). Silencing of acetyl-CoA carboxylase in Heterodera schachtii by RNAi mimicked the effects of spitrotetramat-enol, indicating that the mode-of-action is inhibition of acetyl-CoA carboxylase ( Gutbrod et al, 2018 ).…”

“…The nematicide also inhibits acetyl-CoA carboxylase activity, storage of lipids, fatty acid composition, and disruption of surface coat synthesis in C. elegans ( Gutbrod et al, 2018 ). Silencing of acetyl-CoA carboxylase in Heterodera schachtii by RNAi mimicked the effects of spitrotetramat-enol, indicating that the mode-of-action is inhibition of acetyl-CoA carboxylase ( Gutbrod et al, 2018 ). Concentrations of spirotetramat-enol necessary to result in 95% of a C. elegans population having arrested development were 44 to 48 ppm ( Vang et al, 2016 ).…”