Ciências Biológicas e da Saúde

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    Physiological and molecular basis of spatial repellency mediated by pyrethrum and pyrethroids in Aedes-aegypti
    (Universidade Federal de Viçosa, 2021-02-12) Andreazza, Felipe; Oliveira, Eugênio Eduardo de; http://lattes.cnpq.br/2992672572696736
    Aedes aegypti mosquitoes are vectors of several viruses, such the ones causing Dengue and Yellow fevers, Chikungunya and Zika. Thus, compounds that can repel mosquitoes are used to prevent human-mosquito contact, aiding the fight against vector-borne diseases. Pyrethrum and its synthetic analogs, pyrethroids, are widely used for this purpose. However, the physiological and molecular mechanism of their spatial repellency (i.e., non-contact repellency) have not yet being deciphered. In this thesis, I bring two major contributions to the field, divided into two chapters. In the chapter 1, I present a continuing effort for understanding pyrethrum spatial repellency. As previous studies had shown that the activation of the odorant receptor (Or) protein AaOr31 by a minor component of pyrethrum [i.e., E)-β-farnesene (EBF)] only partially explain the pyrethrum repellency, I showed that pyrethrins I and II, the major components of this extract, elicit repellency by acting in two targets, the voltage-gated sodium channels and an Or expressed in a specific sensilla (i.e., sst-1) in Ae. aegypti antenna. Interesting, I also discovered that pyrethrins action on the voltage-gated sodium channels are responsible for enhancing the EBF repellency, explaining why EBF plays a role in pyrethrum repellency even at minute concentrations. In the chapter 2, I bring a contribution toward understanding the spatial repellency by transfluthrin, one of the main pyrethroids being recently deployed as mosquito repellent. Similarly to pyrethrins, transfluthrin elicits repellency by acting on the voltage-gated sodium channel. However, transfluthrin could not activate any neuron in mosquito major sensing appendages, as well as its repellency does not in-volve activation of any Or. Transfluthrin also enhances repellency of other Or-dependent repellents, including the gold-standard repellent DEET. In fact, I discovery that samples of commercial transfluthrin-based mosquito repellents elicit Or-mediated repellency, even though transfluthrin does not act on Ors. Together, these chapters illustrate that humans have been unknowingly exploiting this dual target synergistic mechanism for insect repellency for centuries, and that single action on voltage-gated sodium channels is sufficient to elicit repellency in Ae. aegypti. These results should inspire new chemistries toward volatile compounds acting on sodium channels and development of potent multi-target mixtures. The reduction in the concentration of individual components when in a mixture is expected to decrease environment contamination, and allergies, such as caused by high concentrations of DEET. There- fore, this new framework to be exploited promotes environmental and social sustainability, and aid the control of deadly vector-born human diseases. Keywords: Mosquitoes. Vector-borne diseases. Behavior. Voltage-gated sodium channels. Odorant receptors. Synergism.