The oviposition cue indole inhibits animal-host attraction in Aedes aegypti (Diptera: Culicidae) mosquitoes

Abstract

Background Mosquitoes represent a major source of disease transmission worldwide. They possess the uncanny ability to discriminate between different ecological resources, including nectar sources, animal-hosts, and oviposition sites, a feature mediated by their exquisite olfactory system. Insect repellents such as N,N-Diethyl-meta-toluamide, also called DEET, have been shown to activate and inhibit mosquito odorant receptors, resulting in behavioral modulation. This and other repellents available for personal protection against mosquitoes are topically applied on the skin and operate at a short range. In our search for potential long-range inhibitors of human-host attractants, we have hypothesized that the shared chemical similarities between indole and DEET may confer the former the ability to block odorant receptor function and inhibit human-host attraction. Methods We used the two-electrode voltage clamp of Xenopus laevis oocytes as a pharmacological platform, to compare the pharmacological effect of commercially-available insect repellents and indole on the Aedes aegypti (R)-1-octen-3-ol receptor OR8, a receptor involved in the decision of female mosquitoes to identify human hosts. We conducted an arm-in-a-cage and a wind-tunnel bioassays to explore the effect of indole on human-host seeking female Aedes aegypti mosquitoes. Results We provide evidence that indole inhibits the Aedes aegypti (R)-1-octen-3-ol receptor OR8, a receptor involved in the decision of female mosquitoes to identify human hosts. In our arm-in-a-cage assay, one molar DEET reduced mosquito visits on average by 69.3% while the same indole concentration achieved 97.8% inhibition. This effect of indole on flight visits was dose-dependent and disappeared at one micromolar. In our long-range bioassay, indole elicited on average 27.5% lower speed, 42.3% lower upwind velocity and 30.4% higher tortuosity compared to our synthetic blend. Conclusions Indole significantly inhibits OR8 activation by (R)-1-octen-3-ol, mosquito visits to a human hand, and long-range human-host seeking. The volatility of indole may be leveraged to develop a novel insect repellent in the context of personal mosquito.