An artistic rendition of mosquitoes avoiding a volatile plume of the newly discovered repellents whose chemical structures are shown.
Credit: Pinky Kain
The insect repellent DEET has been used for 60 years yet no one has been sure how it works. “We wanted to solve the mystery,” says Anandasankar Ray at the University of California, Riverside. In a paper just out in Nature, Ray and colleagues describe finding the olfactory receptors in fruit flies that responds to DEET. Their finding also led them to design more effective insect repellents.
DEET (chemical name: N,N-diethyl-meta-toluamide) was developed by the U.S. Army in 1946. These days, about 140 products containing DEET are registered with the U.S. Environmental Protection Agency. When applied to the skin in the form of a lotion or spray, DEET repels mosquitoes and ticks. These insects are capable of transmitting diseases such as malaria and Lyme.
But DEET has its drawbacks. It’s not effective for disease control in endemic areas, such as Africa, because it is unaffordable and inconvenient to use. It also dissolves some plastics, synthetic fabrics and painted surfaces. More worrisome, there are reports of DEET-resistance in some flies and mosquitoes.
But because researchers are not sure how DEET works, they have had trouble figuring out alternatives to it. Ray and colleagues embarked on a screening assay to search for neurons that are activated by DEET. They used a transgenic Drosophila model in which a fluorescent protein got turned on when cells were activated by a stimulus. These flies were developed by Jing Wang’s group at the University of California, San Diego.
Ray’s team discovered a highly conserved receptor called Ir40a that sits in the DEET-activated neurons in a sac-like structure called the sacculus in the fruit fly antenna. This receptor is turned on by DEET. The neurons in which Ir40a resided are not well understood because they are hard to reach. Identification of the receptor and its location will help the investigators understand how DEET works in the olfactory system. They have already been able to confirm previous reports which demonstrate that DEET acts on the bitter taste pathway in insects.
Ray says now that they know the identity of the DEET receptor, “this opens the possibility of applying modern screening technologies to identify better repellents.” Indeed, that’s what the investigators did next. They developed an assay where they screened more than 400,000 compounds that were similar to DEET and picked out more 100 naturally occurring compounds that looked promising.
The investigators tested 10 of these compounds on fruit flies and found that they activated the neurons with Ir40a and repelled them. Extensive testing of four of these compounds in mosquitoes showed them to be strong repellents. Ray says that the compounds they identified could offer cheaper and safer substitutes that smell pleasant, like grapes.
