Pyrethrins elicit olfactory response and spatial repellency in Aedes albopictus.

Pyrethrum from dry flowers of Chrysanthemum is a well-known botanical insecticide and repellent. Its insecticidal activity attributes to its six insecticidal esters, collectively known as pyrethrins. Pyrethrins and its synthetic analogs pyrethroids exert their toxic action by modifying the function of voltage-gated sodium channels. Aside from insecticidal activity, pyrethrum has also been used to repel mosquitoes for centuries. Today, pyrethrum continues to be used as an active ingredient in mosquito coils and other mosquito-repellent devices globally. However, the mechanism of pyrethrum repellency remains largely unknown. Here we report that pyrethrum vapor induced spatial (non-contact) repellency in Aedes albopictus, a major vector of dengue and West Nile viruses. Using electroantennogram (EAG) recordings from adult antennae, we found that pyrethrum elicited EAG response in a dose-dependent manner. We then isolated the six insecticidal esters, pyrethrins I and II, cinerins I and II, jasmolins I and II from pyrethrum extract and discovered that five of the six esters, except jasmolin I, all elicited EAG responses. Furthermore, pyrethrins I and II, cinerin II and jasmolin II induced repellency, whereas cinerin I and jasmolin I did not. Of the six pyrethrins, four of them, pyrethrins I and II, cinerin II and jasmolin II, activate olfactory-receptor neurons and elicit spatial repellency in Ae. albopictus. Our study provided a foundation for future structure-function studies of pyrethrins, their cognate olfactory receptors and efficacies of repellency and for the development of new and more effective mosquito repellents for controlling vector-borne human diseases. © 2021 Society of Chemical Industry.

Yan R ，Zhou Q ，Xu Z ，Wu Y ，Zhu G ，Wang M ，Guo Y ，Dong K ，Chen M ... -  《-》

A dual-target molecular mechanism of pyrethrum repellency against mosquitoes.

Liu F ，Wang Q ，Xu P ，Andreazza F ，Valbon WR ，Bandason E ，Chen M ，Yan R ，Feng B ，Smith LB ，Scott JG ，Takamatsu G ，Ihara M ，Matsuda K ，Klimavicz J ，Coats J ，Oliveira EE ，Du Y ，Dong K ... -  《Nature Communications》

Bioallethrin activates specific olfactory sensory neurons and elicits spatial repellency in Aedes aegypti.

Use of pyrethroid insecticides is a pivotal strategy for mosquito control globally. Commonly known for their insecticidal activity by acting on voltage-gated sodium channels, pyrethroids, such as bioallethrin and transfluthrin, are used in mosquito coils, emanators and other vaporizers to repel mosquitoes and other biting arthropods. However, whether specific olfactory receptor neurons are activated by pyrethroids to trigger spatial repellency remains unknown. We used behavioral and electrophysiological approaches to elucidate the mechanism of bioallethrin repellency in Aedes aegypti, a major vector of dengue, yellow fever, Zika and chikungunya viruses. We found that bioallethrin elicits spatial (i.e. non-contact) repellency and activates a specific type of olfactory receptor neuron in mosquito antennae. Furthermore, bioallethrin repellency is significantly reduced in a mosquito mutant of Orco, an obligate olfactory co-receptor that is essential for the function of odorant receptors (Ors). These results indicate that activation of specific Or(s) by bioallethrin contributes to bioallethrin repellency. In addition, bioallethrin repellency was reduced in a pyrethroid-resistant strain that carries two mutations in the sodium channel gene that are responsible for knockdown resistance (kdr) to pyrethroids, indicating a role of activation of sodium channels in bioallethrin repellency. Results from this study show that bioallethrin repellency is likely to be the result of co-activation of Or(s) and sodium channels. These findings not only contribute to our understanding of the modes of action of volatile pyrethroids in spatial repellency, but also provide a framework for developing new repellents based on the dual-target mechanism revealed. © 2021 Society of Chemical Industry.

Valbon W ，Andreazza F ，Oliveira EE ，Liu F ，Feng B ，Hall M ，Klimavicz J ，Coats JR ，Dong K ... -  《-》

Identification of multiple odorant receptors essential for pyrethrum repellency in Drosophila melanogaster.

Wang Q ，Xu P ，Andreazza F ，Liu Y ，Nomura Y ，Duran P ，Jiang L ，Chen M ，Takamatsu G ，Ihara M ，Matsuda K ，Isaacs R ，Oliveira EE ，Du Y ，Dong K ... -  《PLoS Genetics》

Action of six pyrethrins purified from the botanical insecticide pyrethrum on cockroach sodium channels expressed in Xenopus oocytes.

Pyrethrin I, pyrethrin II, cinerin I, cinerin II, jasmolin I and jasmolin II are six closely related insecticidal active esters, known as pyrethrins, found in the pyrethrum extract from the dry flowers of Tanacetum cinerariifolium. The chemical structures of the six compounds differ only in the terminal moieties at the acid and alcohol ends, but the compounds' in vivo toxicities are substantially different. Pyrethrins are lead compounds for pyrethroids, a large family of synthetic insecticides that alter nerve functions by prolonging the opening of voltage-gated sodium channels. However, data on the mechanism of action of natural pyrethrins are very limited. In this study, we examined the actions of all six pyrethrins on cockroach sodium channels expressed in Xenopus oocytes. Although the six compounds showed comparable potencies in inhibiting the inactivation of sodium channels, they had greatly variable potencies in inhibiting channel deactivation. Furthermore, unlike pyrethroids, the action of pyrethrins neither depend on nor were enhanced by repeated channel activation. We created a NavMs-based model of the cockroach sodium channel, in which pyrethrin II was docked at the pyrethroid receptor site 1 (PyR1), and proposed a rationale for the observed structure-activity relationship of the six pyrethrins. Our study sheds light on the molecular mechanism of pyrethrum action on sodium channels and reveled differences in the modes of action of the six bioactive constitutes of pyrethrum.

Chen M ，Du Y ，Zhu G ，Takamatsu G ，Ihara M ，Matsuda K ，Zhorov BS ，Dong K ... -  《-》