Sodium channel activation underlies transfluthrin repellency in Aedes aegypti

Abstract

Background Volatile pyrethroid insecticides, such as transfluthrin, have received increasing attention for their potent repellent activities in recent years for controlling human disease vectors. It has been long understood that pyrethroids kill insects by promoting activation and inhibiting inactivation of voltage-gated sodium channels. However, the mechanism of pyrethroid repellency remains poorly understood and controversial. Methodology/Principal findings Here, we show that transfluthrin repels Aedes aegypti in a hand-in-cage assay at nonlethal concentrations as low as 1 ppm. Contrary to a previous report, transfluthrin does not elicit any electroantennogram (EAG) responses, indicating that it does not activate olfactory receptor neurons (ORNs). The 1S-cis isomer of transfluthrin, which does not activate sodium channels, does not elicit repellency. Mutations in the sodium channel gene that reduce the potency of transfluthrin on sodium channels decrease transfluthrin repellency but do not affect repellency by DEET. Furthermore, transfluthrin enhances DEET repellency. Conclusions/Significance These results provide a surprising example that sodium channel activation alone is sufficient to potently repel mosquitoes. Our findings of sodium channel activation as the principal mechanism of transfluthrin repellency and potentiation of DEET repellency have broad implications in future development of a new generation of dual-target repellent formulations to more effectively repel a variety of human disease vectors.

Spatial repellents transfluthrin and metofluthrin affect the behavior of Dermacentor variabilis, Amblyomma americanum, and Ixodes scapularis in an in vitro vertical climb assay

“…Repellents can be further classified by their mode of action as contact and spatial repellents depending on whether a target must contact a treated surface or react by non-tactile means to the volatilized state [29][30][31]. Active ingredients derived from synthetic pyrethroids are frequently used as spatial repellents against vectors that cover large distances, such as mosquitoes and biting flies [32,33]. The efficacy of these spatial repellents is dependent on inherent arthropod sensitivity and the ability to maintain a consistent vapor phase concentration, which is often managed with controlled release devices (CRDs) that modulate dispersion [34][35][36].…”

Implications of Sublethal Insecticide Exposure and the Development of Resistance on Mosquito Physiology, Behavior, and Pathogen Transmission

“…aegypti adults by acting solely on the voltage-gated sodium channels. Transfluthrin-mediated repellency is a likely result of insecticide actions in selected neuronal circuits [142]. Similar repellency mediated by the activation of sodium channels has also been demonstrated for natural pyrethrins [143].…”

Vapor phase repellency and insecticidal activity of pyridinyl amides against anopheline mosquitoes

“… Liu et al. (2013) have reported weak olfactory responses of Culex quinquefasciatus to permethrin and allethrin in single sensillum recordings, and a recent study with transfluthrin found no significant EAG response to this compound, with previous positive results possibility related to impurities ( Andreazza et al., 2021 ). Yang et al.…”