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.

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.

Metrics

  • 2,713
    views
  • 508
    downloads
  • 41
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  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

Share this article

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

Further reading

    1. Developmental Biology
    2. Ecology
    Stav Talal, Jon F Harrison ... Arianne J Cease
    Research Article

    Organisms require dietary macronutrients in specific ratios to maximize performance, and variation in macronutrient requirements plays a central role in niche determination. Although it is well recognized that development and body size can have strong and predictable effects on many aspects of organismal function, we lack a predictive understanding of ontogenetic or scaling effects on macronutrient intake. We determined protein and carbohydrate intake throughout development on lab populations of locusts and compared to late instars of field populations. Self-selected protein:carbohydrate targets declined dramatically through ontogeny, due primarily to declines in mass-specific protein consumption rates which were highly correlated with declines in specific growth rates. Lab results for protein consumption rates partly matched results from field-collected locusts. However, field locusts consumed nearly double the carbohydrate, likely due to higher activity and metabolic rates. Combining our results with the available data for animals, both across species and during ontogeny, protein consumption scaled predictably and hypometrically, demonstrating a new scaling rule key for understanding nutritional ecology.

    1. Ecology
    2. Evolutionary Biology
    Zhixian Zhang, Jianying Li ... Songdou Zhang
    Research Article

    Seasonal polyphenism enables organisms to adapt to environmental challenges by increasing phenotypic diversity. Cacopsylla chinensis exhibits remarkable seasonal polyphenism, specifically in the form of summer-form and winter-form, which have distinct morphological phenotypes. Previous research has shown that low temperature and the temperature receptor CcTRPM regulate the transition from summer-form to winter-form in C. chinensis by impacting cuticle content and thickness. However, the underling neuroendocrine regulatory mechanism remains largely unknown. Bursicon, also known as the tanning hormone, is responsible for the hardening and darkening of the insect cuticle. In this study, we report for the first time on the novel function of Bursicon and its receptor in the transition from summer-form to winter-form in C. chinensis. Firstly, we identified CcBurs-α and CcBurs-β as two typical subunits of Bursicon in C. chinensis, which were regulated by low temperature (10 °C) and CcTRPM. Subsequently, CcBurs-α and CcBurs-β formed a heterodimer that mediated the transition from summer-form to winter-form by influencing the cuticle chitin contents and cuticle thickness. Furthermore, we demonstrated that CcBurs-R acts as the Bursicon receptor and plays a critical role in the up-stream signaling of the chitin biosynthesis pathway, regulating the transition from summer-form to winter-form. Finally, we discovered that miR-6012 directly targets CcBurs-R, contributing to the regulation of Bursicon signaling in the seasonal polyphenism of C. chinensis. In summary, these findings reveal the novel function of the neuroendocrine regulatory mechanism underlying seasonal polyphenism and provide critical insights into the insect Bursicon and its receptor.