Posted on behalf of Marian Turner
Mosquitoes assault our senses with their buzzing and their itchy bites, but we can get back at them by messing with their sense of smell. According to a paper published today in Nature, the chemical DEET, often used in insect repellents, works by confusing the odour code insects use to locate their food.
Scientists already suspected that DEET (N,N-diethyl-meta-toluamide) affects insects’ olfactory systems, either by blocking the insects’ ability to recognize a food target by smell, or by actively repulsing them.
But Leslie Vosshall at the Rockefeller University in New York and her colleagues now think that neither idea tells the full story. Instead, their new data show that DEET interferes with the normal activity of smell-sensing neurons in insect antennae, which Vosshall says are the equivalent of their noses. The insects receive scrambled messages about the odours around them, so they are less effectively attracted to their target.
The researchers recorded the electrical activity of four olfactory neurons in the fruitfly Drosophila melanogaster, which is also affected by DEET. The chemical on its own barely triggered the neurons, but when the researchers combined it with 10 different odours, they saw that DEET sometimes inhibited neuron activity, sometimes enhanced it and sometimes had no effect at all.
“The fact that DEET alone didn’t strongly stimulate any neurons shows us that the chemical confuses the insect, rather than disgusting it,” says Vosshall.
Working from previous studies showing that genetic differences affect sensitivity to smells in humans, a member of Vosshall’s team gambled that natural strains of Drosophila might show different sensitivities to DEET, and started screening strains from around the world. Only 18 strains later, the scientists identified one that wasn’t affected by DEET, although its responses to odours were otherwise normal.
“It was serendipity,” says Vosshall. “The chances of finding a strain like this were next to zero, so it’s just jaw-droppingly cool.”
The team found that an odorant receptor on the olfactory neurons in the insensitive flies differs from the receptors in sensitive strains by just one amino acid, but they think this is enough to make the flies insensitive to DEET.
“This shows us that DEET can directly interact with odorant receptors,” says Vosshall. She points out it is a Drosophila receptor, so their finding doesn’t explain exactly how DEET works in mosquitoes, “but the results have inspired us to look for other molecules that act on these receptors.”
Of course, blood-feeding insects like mosquitoes aren’t just bothersome — they also transmit diseases like malaria and dengue fever, adding importance to the search for effective insect repellents.
DEET has been used for more than 50 years, and Vosshall’s team would like to find a new chemical that is safer and can be used at lower doses. They are now screening random chemical libraries for such molecules. “What we’d like to find is a chemical that shuts down the whole mosquito olfactory system,” says Vosshall, adding “and we’ve got some really good leads.” Look who’s buzzing now.