Background Mosquitoes are responsible for disease transmission worldwide. They possess the ability to discriminate between different ecological resources, including nectar sources, animal hosts and oviposition sites, a feature mediated by their 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 currently available for personal protection against mosquitoes are topically applied to the skin and operate at a short range. In our search for potential long-range inhibitors of attractants to human hosts, we have hypothesized that the shared chemical similarities between indole and DEET may confer the former with the ability to block odorant receptor function and inhibit human host attraction in a similar way as DEET. Methods We used the two-electrode voltage clamp system to assay Xenopus laevis oocytes as a 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-making of female mosquitoes to identify human hosts. We also conducted arm-in-a-cage and wind-tunnel bioassays to explore the effect of indole on human host-seeking female Aedes aegypti mosquitoes. Results Our results demonstrate that indole inhibited the Aedes aegypti (R)-1-octen-3-ol receptor OR8. In our arm-in-a-cage assay, 1 M of 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 1 μM. In the flight tunnel, indole elicited on average 27.5% lower speed, 42.3% lower upwind velocity and 30.4% higher tortuosity compared to the control. 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 protection. Graphical 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.
Mosquitoes represent a major source of disease transmission and possess the uncanny ability to locate suitable animal-hosts, 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 odorant repellents, 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. Using the two-electrode voltage clamp of Xenopus laevis oocytes as a pharmacological platform, 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. Coincidentally, behavioral experiments in an arm-in-cage and flight tunnel assays suggest that indole inhibits animal-host seeking behavior in female Aedes aegypti. Together, our findings suggest that indole may be a candidate spatial repellent for the long-range protection of humans against mosquito bites.
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