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

Lei Guo,Xin-Yu Fan,Xiaomu Qiao,Craig Montell,Jia Huang

doi:10.7554/elife.68268

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 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.

Highlights

The western honeybee, Apis mellifera, is the most common and important pollinator
Factors that appear to contribute to colony collapse disorder and global bee decline include land‐use intensification, pesticides (Martin et al, 2012; Woodcock et al, 2017), and the parasitic mite Varroa destructor, which transmits pathogens (Stokstad, 2019; Wilfert et al, 2016)
It is important to find out why tau-fluvalinate, coumaphos, and amitraz are all effective for Varroa mites but have low toxicity to honeybees

Summary

Introduction

The western honeybee, Apis mellifera, is the most common and important pollinator. They visit flowering plants to collect nectar and move pollen between flowers. It is important to find out why tau-fluvalinate, coumaphos, and amitraz are all effective for Varroa mites but have low toxicity to honeybees. There are at least four classes of OA receptors: Octα1R (α1-a drenergic-like octopamine receptor, referred to as OAMB or OA1), Octα2R (α2-adrenergic- like octopamine receptor, referred to as OA3), OctβR (β-adrenergic-like octopamine receptor, referred to as OA2), and Oct-T yrR (octopamine/tyramine receptor, referred to as TAR1) (Qi et al, 2017) It is not known which one is the molecular target of amitraz in vivo. Our results reveal the molecular target of amitraz in vivo and key residues involved in the selectivity of amitraz between Varroa mites and honeybees. We suggest that our findings will be very useful for resistance management and the design of bee-friendly insecticides

Results

Discussion

Materials and methods

Funding Funder