Methionine can reduce the sublethal risk of Chlorantraniliprole to honeybees (Apis mellifera L.): Based on metabolomics analysis.

Bees, essential for pollination in agriculture and global economic growth. However, the great wax moth (Galleria mellonella, GWM), a Lepidopteran insect, poses a substantial threat to bee colonies, contributing to a global decline in bee populations. Chlorantraniliprole (CH) is one of the primary insecticide used to control GWM due to its efficacy and low toxicity to bees. To improve beekeeping safety and reduce the risk of GWM developing resistance to prolonged use of CH, we investigated the potential of combining methionine (MET) which has been found to have insecticidal activity against certain Lepidoptera pests, with chlorantraniliprole for use in the apiculture industry. This study assessed the combined effects of MET and CH on GWM and honeybees by employing the maximum concentration of MET (1 %, w/w), previously reported as safe for honeybees, and the practical concentration of CH (1 mg/kg) for GWM control. The results revealed limited acute lethal toxicity of MET to GWM and honeybees, whereas the combined chronic exposure of MET and CH (MIX) led to significant synergistic lethal effects on GWM mortality. Nevertheless, the protective effect of MET on honeybees exposed to CH was significant under chronic exposure. Potential mechanisms underlying the synergistic actions of MET and CH may stem from MET-induced protection of the "Cysteine and methionine" and the "Glycine, serine, and threonine" metabolism pathways. Furthermore, immune stress mitigation was also observed in honeybee immune-related gene transcripts treated by the combination of MET and CH under both acute and chronic exposure. The effects of MET on CH activity in GWM and honeybees are likely due to metabolic regulation. This study suggests the potential of developing MET as a promising biopesticide or protective agent in the future.