Mosquito-borne diseases kill about 700,000 people every year. Insect repellents, such as pyrethrum, a chrysanthemum flower extract that humans have used for thousands of years, can save lives. A new study in Nature Communications finally shows how pyrethrum works, with two components acting synergistically to deter the pesky bloodsuckers.
Mosquitoes develop resistance to repellents over time, according to the study’s senior author, Duke University neurotoxicologist Ke Dong. As a result, “new, alternative ones must be constantly developed to eventually replace current ones,” she says. Understanding repellent mechanisms could help. “We’re very excited because we are finally beginning to understand how a popular natural insect repellent, used worldwide, keeps mosquitoes from biting people.”
Dong and her colleagues attached tiny electrodes to hairs on mosquito antennae to study the effects of pyrethrum. They were able to measure the insects’ responses to repellents at the level of individual odorant receptors in nerve cells as a result of this. Many disease-carrying mosquito species have more than 100 such receptors, but the researchers discovered that pyrethrum activates one in particular called Or31—and they confirmed that mosquitos would not flinch if they were genetically modified to lack that receptor.
Dong claims that, unlike many other odorant receptors, Or31 is found in all known disease-carrying mosquito species. Furthermore, unlike pyrethrum, many other natural repellents work by activating multiple odorant receptors, and researchers still know very little about how those other receptors work. Given these considerations, the scientists believe that Or31 could serve as a clear, universal target for developing better repellents.
The researchers also used chemical analysis to figure out how two of pyrethrum’s molecular components, EBF and pyrethrin, cause the repellent response. Mosquito experiments revealed that the chemicals work best together: EBF activates Or31, and pyrethrins increase repellency by intensifying nerve signalling.
Dong and her colleagues intend to investigate the neural circuits underlying the repellency induced by pyrethrum and other natural substances in the future. They will also continue to test other potential repellent molecules, such as the active ingredient in citronella oil, which they discovered also activates Or31.
The findings, according to Johns Hopkins University neuroscientist Christopher Potter, who specialises in insect olfaction and was not involved in the study, could eventually help create “super mosquito repellents.” Untangling which neurons determine mosquito responses to specific odours, in particular, Potter believes, could reveal novel ways to manipulate their behaviour. “Perhaps one day,” he speculates, “we’ll figure out how to turn this dial up even higher or how to trick mosquitos into becoming repelled by other odors—like those that normally attract them to humans.”
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