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Molecular basis of selective resistance of the bumblebee BiNav1 sodium channel to tau-fluvalinate.

Publication ,  Journal Article
Wu, S; Nomura, Y; Du, Y; Zhorov, BS; Dong, K
Published in: Proceedings of the National Academy of Sciences of the United States of America
December 2017

Insecticides are widely used to control pests in agriculture and insect vectors that transmit human diseases. However, these chemicals can have a negative effect on nontarget, beneficial organisms including bees. Discovery and deployment of selective insecticides is a major mission of modern toxicology and pest management. Pyrethroids exert their toxic action by acting on insect voltage-gated sodium channels. Honeybees and bumblebees are highly sensitive to most pyrethroids, but are resistant to a particular pyrethroid, tau-fluvalinate (τ-FVL). Because of its unique selectivity, τ-FVL is widely used to control not only agricultural pests but also varroa mites, the principal ectoparasite of honeybees. However, the mechanism of bee resistance to τ-FVL largely remains elusive. In this study, we functionally characterized the sodium channel BiNav1-1 from the common eastern bumblebee (Bombus impatiens) in Xenopus oocytes and found that the BiNav1-1 channel is highly sensitive to six commonly used pyrethroids, but resistant to τ-FVL. Phylogenetic and mutational analyses revealed that three residues, which are conserved in sodium channels from 12 bee species, underlie resistance to τ-FVL or sensitivity to the other pyrethroids. Further computer modeling and mutagenesis uncovered four additional residues in the pyrethroid receptor sites that contribute to the unique selectivity of the bumblebee sodium channel to τ-FVL versus other pyrethroids. Our data contribute to understanding a long-standing enigma of selective pyrethroid toxicity in bees and may be used to guide future modification of pyrethroids to achieve highly selective control of pests with minimal effects on nontarget organisms.

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Published In

Proceedings of the National Academy of Sciences of the United States of America

DOI

EISSN

1091-6490

ISSN

0027-8424

Publication Date

December 2017

Volume

114

Issue

49

Start / End Page

12922 / 12927

Related Subject Headings

  • Xenopus laevis
  • Voltage-Gated Sodium Channels
  • Voltage-Gated Sodium Channel Blockers
  • Pyrethrins
  • Protein Conformation, alpha-Helical
  • Nitriles
  • Molecular Docking Simulation
  • Insecticides
  • Insecticide Resistance
  • Insect Proteins
 

Citation

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Wu, S., Nomura, Y., Du, Y., Zhorov, B. S., & Dong, K. (2017). Molecular basis of selective resistance of the bumblebee BiNav1 sodium channel to tau-fluvalinate. Proceedings of the National Academy of Sciences of the United States of America, 114(49), 12922–12927. https://doi.org/10.1073/pnas.1711699114
Wu, Shaoying, Yoshiko Nomura, Yuzhe Du, Boris S. Zhorov, and Ke Dong. “Molecular basis of selective resistance of the bumblebee BiNav1 sodium channel to tau-fluvalinate.Proceedings of the National Academy of Sciences of the United States of America 114, no. 49 (December 2017): 12922–27. https://doi.org/10.1073/pnas.1711699114.
Wu S, Nomura Y, Du Y, Zhorov BS, Dong K. Molecular basis of selective resistance of the bumblebee BiNav1 sodium channel to tau-fluvalinate. Proceedings of the National Academy of Sciences of the United States of America. 2017 Dec;114(49):12922–7.
Wu, Shaoying, et al. “Molecular basis of selective resistance of the bumblebee BiNav1 sodium channel to tau-fluvalinate.Proceedings of the National Academy of Sciences of the United States of America, vol. 114, no. 49, Dec. 2017, pp. 12922–27. Epmc, doi:10.1073/pnas.1711699114.
Wu S, Nomura Y, Du Y, Zhorov BS, Dong K. Molecular basis of selective resistance of the bumblebee BiNav1 sodium channel to tau-fluvalinate. Proceedings of the National Academy of Sciences of the United States of America. 2017 Dec;114(49):12922–12927.
Journal cover image

Published In

Proceedings of the National Academy of Sciences of the United States of America

DOI

EISSN

1091-6490

ISSN

0027-8424

Publication Date

December 2017

Volume

114

Issue

49

Start / End Page

12922 / 12927

Related Subject Headings

  • Xenopus laevis
  • Voltage-Gated Sodium Channels
  • Voltage-Gated Sodium Channel Blockers
  • Pyrethrins
  • Protein Conformation, alpha-Helical
  • Nitriles
  • Molecular Docking Simulation
  • Insecticides
  • Insecticide Resistance
  • Insect Proteins