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
Mosquitoes are the deadliest of all combined insects and animals affecting millions and killing hundreds or thousands of people each year. Existing protection methods however are limited and include volatile compounds that actively repel mosquitoes such as N,N-Diethyl-meta-toluamide (DEET) or different essential oils such as geraniol and citronella. Most are odorous compounds and require organic solvents for dispersion. This work investigates the barrier properties of cellulose nanocrystals (CNCs). CNCs are known to self-assemble in strong, transparent, chemical barrier films. They are fully bio-based, and their surface chemistry is ideal for aqueous dispersion of many compounds. This work saw a significant 80% decrease in feeding on human skin when a thin CNC coat was applied. The effect was further confirmed by artificial feeding on Aedes aegypti wherein CNC appears to act as a chemical camouflage to the many cues sought by the insects. The combined effect of CNC with indole reduced egg laying post exposure to mammalian blood close to null with 99.4% less eggs as compared to control. The chemical barrier effect was assessed through a simple headspace experiment showing that the same CNC coat blocked the passage of ammonium hydroxide vapor, a commonly used mosquito attractant, when applied on a filter paper membrane.
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 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, we also show that indole inhibits the animal-host seeking behavior of female Aedes aegypti. Together, our findings suggests that indole may be a candidate spatial repellent for the long-range protection of humans against mosquito bites.
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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