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Female mosquitoes, which feed on human blood to obtain iron and amino acids required to produce eggs, are notorious for transmitting viruses responsible for deadly diseases, such as yellow fever, Dengue, and Zika. Over the years, researchers have devised various solutions, ranging from repellents to vaccines to genetic engineering, to combat the vectors. Now, a team at New York's Rockefeller University has come up with a unique solution to fend off the dangerous insects - filling their little bellies with diet drugs to curb their appetite for human blood.
For the study, the scientists, led by neurobiologist Leslie Vosshall, picked the Aedes aegypti mosquitoes. The adult females can lay up to five clutches of more than 100 eggs each during their three-week-long lifespan, requiring multiple servings of human blood. This results in numerous opportunities to pass infectious viruses between humans. However, once the females fill up on human blood, they showed no desire to eat again for at least four days.
Vosshall and her team suspected that the neuropeptide Y (NPY) receptors responsible for food-seeking behavior in humans may be present in mosquitoes as well. The scientists wondered if appetite suppressants that work by targeting the NYP receptors in humans could have the same effect on the insects. To test this, they crushed some diet pills and mixed them in a saline solution that contained ATP — a molecule found inside most animal cells that mosquitoes find irresistible. After the mosquitoes had filled up on the concoction, the researchers teased them with a piece of nylon stocking with a strong human odor. While this would typically have drawn in all the insects, the test group showed no interest in the clothing, leading the team to conclude the diet drugs had temporarily curbed the mosquitoes' desire for human blood.
"On a lark, we thought, 'Let's go for it. Let's do the craziest experiment possible and get some human diet drugs and see if they work on mosquitoes,' " Vosshall told NPR. "It was surprising that it worked so well."
To identify the particular receptor that the human drugs were affecting, the scientists recreated all 49 of the species’ possible NPY receptors and exposed each to the same compounds. They found that only one, NPYLR7, reacted to the human drug. To confirm their results, the team fed the drug-infused solution to some Aedes aegypti mosquitoes, which had been genetically modified to lack the NPYLR7 receptor. Sure enough, the human drugs had no impact on the group, which remained hungry for blood.
While the results were encouraging, the scientists knew that the human drug used to manipulate the receptor in the lab wouldn’t be suitable for use in the wild. In addition to being expensive, it could also trigger human receptors and affect people. To resolve the issue, the scientists searched through a catalog of 265,000 readily-available chemicals to find one that would activate the mosquitoes' NPYLR7 receptor without triggering human NPY receptors. After narrowing the list down to 24 possibilities, they found that compound 18 worked like a charm.
"When they’re hungry, these mosquitoes are super motivated. They fly toward the scent of a human the same way that we might approach a chocolate cake,” Vosshall said in a press release. “But after they were given the drug, they lost interest.”
The study, published in the journal Cell on February 9, 2019, is still in its early stages. The researchers need to find a cost-effective way to test the drug in the wild and ensure its release does not adversely affect the ecosystem. However, if successful it would add to our arsenal of ways to prevent these tiny bloodsuckers from spreading disease. "All of these advances are complementary," said Vosshall, who believes no single method can help eradicate mosquito-borne diseases and advocates using several methods at once. "Our behavior control is something else in this portfolio."
Resources: smithsonianmag.com, npr.com, europeanscientist.com