Sniff-n-scratch: How mosquitoes sniff us out

December 5, 2013 § Leave a comment

Image credit: Genevieve Tauxe

Image credit: Genevieve Tauxe

Researchers have figured out how mosquitoes pick up our scents. In a paper just out in the journal Cell, a team led by Anandasarkar Ray at the University of California, Riverside, identified one important class of neurons in mosquitoes that detect our skin odors. The work has implications for developing more effective mosquito traps and repellants in places plagued with mosquito-borne diseases, such as malaria and dengue.

Mosquitoes follow carbon dioxide emitted when we breathe, and, once they get close enough, dive toward our bare skin, attracted by the odors given off there. While the neuron that picked up carbon dioxide had been known, the identity of the neuron or neurons with odor receptors that attracted mosquitoes to human skin scents remained unknown.

Ray says that, for many years, he and his colleagues focused their search for human-skin odor receptors on the complex mosquito antennae, which express numerous members of an olfactory receptor gene family thought to be involved in picking up scents. They ignored the simpler maxillary palp organs, small fingerlike sensory structures, that contain the carbon dioxide receptors. Conventional wisdom was that the carbon dioxide receptor “was narrowly tuned, responding primarily to carbon dioxide,” says Ray.

So imagine the investigators’ surprise when they discovered “the carbon dioxide receptor is an extremely sensitive detector of several skin odorants,” says Ray. “In fact, it is far more sensitive to some of these odor molecules when compared to carbon dioxide.”

The investigators used a variety of techniques, including the use of a wind tunnel filled with mosquitoes flying toward beads coated with a human foot odor, to establish that the carbon dioxide receptor neuron, called cpA, also picked up foot odors.

To see if cpA can be targeted by chemicals that might be developed as mosquito traps, the investigators next screened nearly half a million compounds to find ones that either activated or shut down cpA. They eventually settled on two compounds: ethyl pyruvate, a fruity-smelling cpA inhibitor used as a flavor agent in food, and cyclopentanone, a minty-scented cpA activator used as a flavor and fragrance agent. Ethyl pyruvate substantially reduced the mosquitoes’ attraction toward a human arm, in effect acting as a repellent. Cyclopentanone, meanwhile, lured mosquitoes, so it could be used as an attractant in a trap.

Ray’s group earlier had identified neurons in insects that detect the repellent DEET. That work, explains Ray, can help researchers devise ways to repel mosquitoes. The current work described in the Cell paper can be used to come up with ways to trap mosquitoes or mask the cues that attract them to humans.

Ray already has moved toward developing applications of the latest work. “Parts of this carbon dioxide receptor technology has been licensed to an insect research company called Olfactor Labs hat I helped set up in 2010,” he says. “This research company is performing additional discovery and large-scale screening of the carbon dioxide receptor.” The Kite Patch, a sticker that repels mosquitoes, is one of the company’s products.

Finally figuring out how insect repellent DEET works

October 2, 2013 § 3 Comments

An artistic rendition of mosquitoes avoiding a volatile plume of the newly discovered repellents whose chemical structures are shown.   Credit: Pinky Kain

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.

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