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 ... -  《-》

AsOBP1 is required for bioallethrin repellency in the malaria vector mosquito Anopheles sinensis.

The use of insecticides, primarily pyrethroids, is a pivotal strategy for mosquito control globally. Bioallethrin, the first commercially available volatile pyrethroid, can elicit spatial (i.e., noncontact) repellency to mosquitoes through the coactivation of olfactory receptor neurons and sodium channels. However, the olfactory mechanism of the repellency elicited by bioallethrin in mosquitoes is still unclear. Here, we demonstrated the involvement of AsOBP1 in the bioallethrin repellency in Anopheles sinensis, one of the main vectors of vivax malaria in China and other Southeast Asian countries. The behavioral and electrophysiological analyses in AsOrco-/- mutant found that the spatial repellency elicited by bioallethrin depended on the odorant receptor (OR)-mediated olfactory pathway. Furthermore, the repellency was reduced in the AsOBP1-/- mutant and a pyrethroid-resistant strain, in which the expression of AsOBP1 was significantly decreased. Moreover, recombinant AsOBP1 protein bound to bioallethrin in an in vitro competition assay. These results indicate that activation of the AsOBP1-mediated olfactory pathway is an important component of bioallethrin repellency. Our research lays the foundation for further elucidation into the olfactory mechanism of bioallethrin repellency and the behavioral modifications of pyrethroid-resistant mosquitoes.

Zhang Y ，He S ，He C ，Zhou L ，Xu O ，Qiao L ，Chen B ，Cao Y ，He Z ... -  《-》

Transfluthrin enhances odorant receptor-mediated spatial repellency in Aedes aegypti.

Mosquito-borne diseases are an increasing global health challenge and vector-based interventions remain the most important methods for reducing the public health burden of most mosquito-borne diseases. Transfluthrin, a volatile pyrethroid insecticide, is used widely and effectively as an insecticide and as a repellent. In a recent study, we showed that at very low concentrations transfluthrin repels Aedes aegypti mosquitoes in a hand-in-cage assay without detectable stimulation of antennal olfactory responses. Furthermore, activation of sodium channels by transfluthrin enhances repellency by DEET, which has been reported to repel mosquitoes via odorant receptor (Or)-dependent and Or-independent mechanisms. However, whether activation of sodium channels by transfluthrin can serve as a general mechanism for synergizing the activities of other repellents remain unknown. In this study, we found that, in hand-in-cage assay, transfluthrin enhanced repellency by geranyl acetate and (E)-β-farnesene, which activate AaOr31. Such enhancement was not observed in AaOr31-knockout mosquitoes and dampened in a pyrethroid-resistant strain carrying two sodium channel mutations, which reduce the action of transfluthrin on sodium channels. In addition, transfluthrin also enhanced repellency by (-)-borneol, (±)-citronellal, camphor, and eucalyptol, which activate Or-mediated repellency. Our study has uncovered the ability of transfluthrin to enhance the repellency to a variety of mosquito repellents, beyond DEET, and provided experimental support for the emerging paradigm of synergistic interactions between repellency mediated by sodium channel activation and Or activation. These findings have potential implications in the development of more effective mosquito repellent mixtures.

Andreazza F ，Valbon W ，Dong K 《-》

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 ... -  《-》

Pyrethroid insecticides maintain repellent effect on knock-down resistant populations of Aedes aegypti mosquitoes.

Bowman NM ，Akialis K ，Cave G ，Barrera R ，Apperson CS ，Meshnick SR ... -  《PLoS One》