An octopamine receptor confers selective toxicity of amitraz on honeybees and Varroa mites

The Varroa destructor mite is a devastating parasite of Apis mellifera honeybees. They can cause colonies to collapse by spreading viruses and feeding on the fat reserves of adults and larvae. Amitraz is used to control mites due to its low toxicity to bees; however, the mechanism of bee resistance to amitraz remains unknown. In this study, we found that amitraz and its major metabolite potently activated all four mite octopamine receptors. Behavioral assays using Drosophila null mutants of octopamine receptors identified one receptor subtype Oct beta 2R as the sole target of amitraz in vivo. We found that thermogenetic activation of oct beta 2R-expressing neurons mimics amitraz poisoning symptoms in target pests. We next confirmed that the mite Oct beta 2R was more sensitive to amitraz and its metabolite than the bee Oct beta 2R in pharmacological assays and transgenic flies. Furthermore, replacement of three bee-specific residues with the counterparts in the mite receptor increased amitraz sensitivity of the bee Oct beta 2R, indicating that the relative insensitivity of their receptor is the major mechanism for honeybees to resist amitraz. The present findings have important implications for resistance management and the design of safer insecticides that selectively target pests while maintaining low toxicity to non-target pollinators.

Automated summary

The study revealed that amitraz activates octopamine receptors in Varroa mites, with bees being relatively insensitive to it. Bees resist amitraz through their insensitive receptors, which has implications for resistance management and the development of safer insecticides targeting pests while being less toxic to non-target pollinators.