Studies of an insecticidal inhibitor of acetyl-CoA carboxylase in the nematode C. elegans

We have studied the mode of action of the insecticide spirotetramat in the nematode Caenorhabditis elegans. A combination of symptomology, forward genetics and genome editing show that spirotetramat acts on acetyl-CoA carboxylase (ACC) in C. elegans, as it does in insects. We found C. elegans embryos exposed to spirotetramat show a cell division defect which closely resembles the phenotype of loss-of-function mutations in the gene pod-2, which encodes ACC. We then identified two mutations in the carboxyl transferase domain of pod-2 (ACC) which confer resistance and were confirmed using CRISPR/Cas9. One of these mutations substitutes an invertebrate-specific amino acid with one ubiquitous in other taxa; this residue may, therefore, be a determinant of the selectivity of spirotetramat for invertebrates. Such a mutation may also be the target of selection for resistance in the field. Our study is a further demonstration of the utility of C. elegans in studying bioactive chemicals.