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

  1. Lei Guo
  2. Xin-yu Fan
  3. Xiaomu Qiao
  4. Craig Montell
  5. Jia Huang  Is a corresponding author
  1. Zhejiang University, China
  2. University of California, Santa Barbara, United States

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.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for all the figures.

Article and author information

Author details

  1. Lei Guo

    Institute of Insect Sciences, Zhejiang University, Hangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  2. Xin-yu Fan

    Institute of Insect Sciences, Zhejiang University, Hangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Xiaomu Qiao

    Institute of Insect Sciences, Zhejiang University, Hangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Craig Montell

    Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, Santa Barbara, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5637-1482
  5. Jia Huang

    Institute of Insect Sciences, Zhejiang University, Hangzhou, China
    For correspondence
    huangj@zju.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8336-1562

Funding

National Natural Science Foundation of China (31572039)

  • Jia Huang

National Natural Science Foundation of China (32072496)

  • Jia Huang

Zhejiang Provincial Outstanding Youth Science Foundation (LR19C140002)

  • Jia Huang

National Institute on Deafness and Other Communication Disorders (DC007864)

  • Craig Montell

National Institute on Deafness and Other Communication Disorders (DC016278)

  • Craig Montell

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Sonia Sen, Tata Institute for Genetics and Society, India

Version history

  1. Received: March 10, 2021
  2. Accepted: July 11, 2021
  3. Accepted Manuscript published: July 12, 2021 (version 1)
  4. Version of Record published: July 26, 2021 (version 2)

Copyright

© 2021, Huang et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Lei Guo
  2. Xin-yu Fan
  3. Xiaomu Qiao
  4. Craig Montell
  5. Jia Huang
(2021)
An octopamine receptor confers selective toxicity of amitraz on honeybees and Varroa mites
eLife 10:e68268.
https://doi.org/10.7554/eLife.68268

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https://doi.org/10.7554/eLife.68268

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