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.

蚊媒疾病是日益严重的全球健康挑战，基于病媒的干预措施仍然是减轻大多数蚊媒疾病的公共卫生负担的最重要方法。四氟菊酯是一种挥发性拟除虫菊酯杀虫剂，被广泛有效地用作杀虫剂和驱虫剂。在最近的一项研究中，我们表明，在非常低的浓度下，transfluthrin在手入笼试验中可以驱除埃及伊蚊，而不会检测到触角嗅觉反应的刺激。此外，四氟菊酯激活钠通道可增强避蚊胺的驱避性，​​据报道避蚊胺可通过气味受体 (Or) 依赖性和 Or 独立机制。然而，四氟菊酯激活钠通道是否可以作为协同其他驱虫剂活性的一般机制仍然未知。在这项研究中，我们发现，在笼中手试验中，四氟菊酯增强了乙酸香叶酯和 ( E)-β-法尼烯，激活 AaOr31。这种增强在 AaOr31 敲除蚊子中没有观察到，并且在携带两个钠通道突变的拟除虫菊酯抗性菌株中被抑制，这减少了四氟菊酯对钠通道的作用。此外，四氟菊酯还增强了 (−)-冰片、(±)-香茅醛、樟脑和桉叶素的排斥性，它们激活了 Or 介导的排斥性。我们的研究揭示了除避蚊胺之外，四氟菊酯增强对多种驱蚊剂的驱避性的能力，并为钠通道激活和 Or 激活介导的驱避性之间的协同相互作用的新兴范式提供了实验支持。这些发现对开发更有效的驱蚊混合物具有潜在影响。