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Odour receptors and neurons for DEET and new insect repellents

A Retraction to this article was published on 22 June 2016

Abstract

There are major impediments to finding improved DEET alternatives because the receptors causing olfactory repellency are unknown, and new chemicals require exorbitant costs to determine safety for human use. Here we identify DEET-sensitive neurons in a pit-like structure in the Drosophila melanogaster antenna called the sacculus. They express a highly conserved receptor, Ir40a, and flies in which these neurons are silenced or Ir40a is knocked down lose avoidance to DEET. We used a computational structure–activity screen of >400,000 compounds that identified >100 natural compounds as candidate repellents. We tested several and found that most activate Ir40a+ neurons and are repellents for Drosophila. These compounds are also strong repellents for mosquitoes. The candidates contain chemicals that do not dissolve plastic, are affordable and smell mildly like grapes, with three considered safe in human foods. Our findings pave the way to discover new generations of repellents that will help fight deadly insect-borne diseases worldwide.

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Figure 1: DEET is detected by Ir40a+ sacculus neurons.
Figure 2: Ir40a neurons detect DEET and are required for repellency.
Figure 3: Ir40a is required for DEET avoidance.
Figure 4: Chemical informatics prediction of new repellents.
Figure 5: Predicted repellents activate Ir40a neurons and are strong repellents for Drosophila.
Figure 6: A new class of mosquito repellents with desirable safety profiles.

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Acknowledgements

We thank A. Ganguly and D. Carter for help with calcium imaging; Z. Wisotsky for help with gustatory experiments; D. MacWilliam for help with olfactory experiments; J. Wang for sharing the NFAT transgenic fly line; and R. Benton for sharing the Ir40a-Gal4 fly line. This work was partly funded by a Whitehall Foundation grant to A.D., an R21NS074332 (NINDS) to A.D. and A.R., and an R56AI099778 (NIAID) and R01AI087785 (NIAID) to A.R. The granting agencies had no role in experimental design or analysis.

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Authors

Contributions

S.M.B. planned and performed the chemical informatics and solubility experiment, and helped design the behaviour experiments. P.K. planned and performed the NFAT imaging, Ca2+ imaging and Drosophila behaviour experiments. S.K.T. performed Ca2+ imaging, electrophysiology and some behaviour experiments. T.G. performed the arm-in-cage experiments. C.P. performed behaviour analysis. S.M.B., P.K. and S.K.T. helped prepare drafts of the manuscript and figures. A.D. planned experiments and helped write the manuscript. A.R. planned experiments, managed the project, and wrote the manuscript.

Corresponding author

Correspondence to Anandasankar Ray.

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Competing interests

P.K., S.M.B., C.P. and A.R. are listed as inventors in pending patent applications filed by the University of California Riverside.

Supplementary information

Supplementary Information

This file contains Supplementary Figures 1-11 and Supplementary Tables 1-2. (PDF 2933 kb)

DEET activates neurons in the sacculus

This video shows a confocal Z-stack of a representative antenna from LexAop-CD8-GFP-2ACD8-GFP; UAS-mLexA-VP16-NFAT, LexAop-CD2-GFP D. melanogaster exposed to10% DEET (from experiment in Figure 1b). (AVI 505 kb)

BA activates neurons in the sacculus

This video shows a confocal Z-stack of a representative antenna from LexAop-CD8-GFP-2ACD8-GFP; UAS-mLexA-VP16-NFAT, LexAop-CD2-GFP D. melanogaster exposed to 10% BA (from experiment in Figure 5a). (AVI 1436 kb)

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Kain, P., Boyle, S., Tharadra, S. et al. Odour receptors and neurons for DEET and new insect repellents. Nature 502, 507–512 (2013). https://doi.org/10.1038/nature12594

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