A dual-target molecular mechanism of pyrethrum repellency against mosquitoes

Feng Liu,Ke Dong,Felipe Andreazza,Jeffrey G Scott,James Klimavicz,Yuzhe Du,Kazuhiko Matsuda,Bo Feng,Qiang Wang,Ru Yan,Makoto Ihara,Elizabeth Bandason,Joel Coats,Genki Takamatsu,Wilson R Valbon,Eugenio E Oliveira,Mengli Chen,Peng Xu,Leticia B Smith

doi:10.1038/s41467-021-22847-0

Abstract

Pyrethrum extracts from flower heads of Chrysanthemum spp. have been used worldwide in insecticides and repellents. While the molecular mechanisms of its insecticidal action are known, the molecular basis of pyrethrum repellency remains a mystery. In this study, we find that the principal components of pyrethrum, pyrethrins, and a minor component, (E)-β-farnesene (EBF), each activate a specific type of olfactory receptor neurons in Aedes aegypti mosquitoes. We identify Ae. aegypti odorant receptor 31 (AaOr31) as a cognate Or for EBF and find that Or31-mediated repellency is significantly synergized by pyrethrin-induced activation of voltage-gated sodium channels. Thus, pyrethrum exerts spatial repellency through a novel, dual-target mechanism. Elucidation of this two-target mechanism may have potential implications in the design and development of a new generation of synthetic repellents against major mosquito vectors of infectious diseases.

Highlights

Pyrethrum extracts from flower heads of Chrysanthemum spp. have been used worldwide in insecticides and repellents
We found that pyrethrin I (P-I) and pyrethrin II (P-II), two major components purified from pyrethrum extracts (Supplementary Fig. 8), activate sst-1A neurons in Rockefeller mosquitoes (Fig. 5a)
A minor component of pyrethrum, (E)-β-farnesene (EBF), activates aegypti odorant receptor 31 (AaOr31), while Or31-mediated repellency is significantly synergized by pyrethrins, which are activators of voltage-gated sodium channels and the principal components of pyrethrum

Summary

Introduction

Pyrethrum extracts from flower heads of Chrysanthemum spp. have been used worldwide in insecticides and repellents. We find that the principal components of pyrethrum, pyrethrins, and a minor component, (E)-βfarnesene (EBF), each activate a specific type of olfactory receptor neurons in Aedes aegypti mosquitoes. We identify Ae. aegypti odorant receptor 31 (AaOr31) as a cognate Or for EBF and find that Or31-mediated repellency is significantly synergized by pyrethrin-induced activation of voltage-gated sodium channels. Pyrethrum exerts spatial repellency through a novel, dual-target mechanism. Elucidation of this two-target mechanism may have potential implications in the design and development of a new generation of synthetic repellents against major mosquito vectors of infectious diseases. Our study resolved all these questions and revealed a novel, dual-target mechanism for insect repellency, involving dual activation of olfactory repellency pathways and voltage-gated sodium channels. The discovery has significant basic and practical implications in understanding the mechanisms and development of insect repellents against mosquitoes and other human disease vectors

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Conclusion