Mode of action underlying toxicity of Camptothecin to Spodoptera frugiperda (Lepidoptera) larvae

Camptothecin (CPT) is derived from Camptotheca acuminate and its main action is the inhibition of the DNA topoisomerase I (Top I) complex. Therefore, CPT and its derivatives are always used as antitumor and antimicrobial agents and also have some insecticidal effects. However, the mode of action underlying the toxicity of CPT to the virulence of pests is still not fully understood. In this study, the effects of CPT on Spodoptera frugiperda (S. frugiperda) were determined by performing toxicity assessments, metabolomics, and mechanism analysis. The results showed that CPT increased the efficiency of inhibition of larval weight in a dose and time-dependent manner. In addition, the metabolomics of 5th-instar larval hemolymph was determined by UPLC-MS/MS and ¹H NMR analysis. UPLC-MS/MS analysis showed that the energy metabolic pathway was more important than the amino acid pathway for the resistance of S. frugiperda to CPT. Furthermore, metabolites involved in the energy metabolic pathway were analyzed using ¹H NMR, and fumarate and pyruvate were identified as interesting metabolites. Bioassays confirmed that they play a key role in enhancing the resistance of S. frugiperda larvae to CPT. Finally, the underlying mechanisms were found to be related to the restorative effects of the two metabolites on metabolic pathways associated with the TCA cycle. In a word, CPT is a potential biological insecticide that exhibits a strong toxicological effect against S. frugiperda by inhibiting the TCA cycle, which provides theoretical support for applying CPT in the control of pests.