Scientists Find Insect DEET Receptors, Develop Safe Alternatives to DEET

UC Riverside research has large implications for controlling insect-borne diseases worldwide

Insects are repelled by N,N-diethyl-m-toluamide, also known as DEET.  But exactly which olfactory receptors insects use to sense DEET has eluded scientists for long.

Now researchers at the University of California, Riverside have identified these DEET-detecting olfactory receptors that cause the repellency — a major breakthrough in the field of olfaction.

Further, the team of researchers has identified three safe compounds that mimic DEET and could one day be used to prevent the transmission of deadly vector-borne diseases such as malaria, dengue, West Nile virus, and yellow fever.

Study results appear online Oct. 2 in Nature.

“Until now, no one had a clue about which olfactory receptor insects used to avoid DEET,” said Anandasankar Ray, an associate professor of entomology, who led the research team.  “Without the receptors, it is impossible to apply modern technology to design new repellents to improve upon DEET.”

The method Ray’s team used to identify the receptors examined in an unbiased fashion all the sensory neurons in the insect, which was the key to successfully finding them.  In their experiments, the researchers used the genetic model system Drosophila melanogaster  (fruit fly) that was genetically engineered in such a way that neurons activated by DEET glowed fluorescent green.  The researchers thus found the receptors, called Ir40a receptors, lining the inside of a poorly studied region of the antenna called the sacculus.

Introduced in the 1940s, DEET has remained unchanged for the past 65 years largely because the receptor in insects for DEET was unknown. Capable of dissolving plastics and nylon, DEET has been reported to inhibit an enzyme (acetylcholinesterase) in mammals that is important in the nervous system. DEET is also unaffordable and inconvenient for use in Africa and other parts of the world where hundreds of millions of people suffer from insect-transmitted diseases.

“Our three compounds, which we tested rigorously in the lab, do not dissolve plastics,” Ray said.   “They are approved by the Food and Drug Administration for consumption as flavors or fragrances, and are already being used as flavoring agents in some foods.  But now they can be applied to bed-nets, clothes, curtains — making them ward off insects.”

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Using novel chemical informatics strategies, Ray’s lab screened half a million compounds against the DEET receptor to identify substitutes.  A computer algorithm the team developed identified which compounds are not only predicted to be strong repellents but also found naturally in fruits, plants or animals.  The algorithm predicted nearly 200 natural DEET substitutes; of which the researchers tested ten compounds.  Of these, eight were strong repellents on flies, of which four were tested in Aedesmosquitoes and found to be strong repellents. Of the four compounds, three are already approved by the Food and Drug Administration as food additives.

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