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

Abstract

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 Octβ2R as the sole target of amitraz in vivo. We found that thermogenetic activation of octβ2R-expressing neurons mimics amitraz poisoning symptoms in target pests. We next confirmed that the mite Octβ2R was more sensitive to amitraz and its metabolite than the bee Octβ2R 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 Octβ2R, indicating that 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.

Pharmacological Properties and Function of the PxOctβ3 Octopamine Receptor in Plutella xylostella (L.)

“…DmOctβ2 is an important target of amitraz, and Drosophila with DmOctβ2 knockouts was unresponsive to amitraz. In contrast, the artificial activation of DmOctβ2 neurons induced amitraz-like poisoning symptoms [ 37 ]. Three β-adrenergic-like octopamine receptors (Octβ1, Octβ2, and Octβ3) are found in D .…”

A novel beta-adrenergic like octopamine receptor modulates the audition of malaria mosquitoes and serves as insecticide target

“…To investigate if the octopaminergic signalling in the mosquito ear is affected by amitraz, we tested its effects on the antennal fibrillae erection. Amitraz activates both α- and β-adrenergic-like receptor octopamine receptors in other insects (47,48), so we would expect it to induce the erection of the antennal fibrillae through its activation of the β-adrenergic-like octopamine receptor AGAP002886.…”

Octopamine receptor genes are involved in the starvation response ofRhopalosiphum padi(Hemiptera: Aphididae)

“…In the phylogenetic tree, RpOAMB and RpOctR were clustered with α‐adrenergic‐like receptors from other insects; RpOctβ1R, RpOctβ2R and RpOctβ3R were clustered into β‐adrenergic‐like receptors; and RpOctR‐like was grouped with tyramine receptor‐like genes. All six OA receptors from R. padi had seven α‐helix transmembrane domains which were typical of GPCRs, which were important in the regulation of multiple insect physiological activities (Guo et al, 2021; Guo et al, 2021; Maqueira et al, 2005). The CWxP motif of three RpOctβRs in the TM6 contained the microswitch Pro, which served as a pivot for the movement of the TM6 during receptor activation (Chelikani et al, 2007; Gujar et al, 2021).…”