March 1, 2010

How Mosquitoes Get a Whiff of Humans

Electron micrograph of a mosquito head Anopheles up close, showing the antennae and feathery mouth parts that contain odor receptors.Janice Carr, Centers for Disease Control and Prevention

By transplanting odor-sensing genes from mosquitoes into frog eggs and fruit flies, scientists have pinpointed dozens of odor receptors that help mosquitoes sniff out their human prey. The findings could lead to new methods for repelling or trapping malaria-spreading mosquitoes through their sense of smell.

Malaria, a disease that kills more than 1 million people each year, is transmitted by the bite of the Anopheles mosquito. The insects follow their victims’ scent via odor receptors found on the mosquito’s antennae and mouth parts. But the molecular basis of this process has been poorly understood.

To learn more about how Anopheles home in on humans, collaborators at Yale University and Vanderbilt University conducted 2 separate but complementary studies. They systematically tested dozens of Anopheles odor receptors for their abilities to detect 110 odorants. Their research was supported by NIH’s National Institute on Deafness and Other Communication Disorders (NIDCD), National Institute of Allergy and Infectious Diseases (NIAID) and the Foundation for NIH through a grant from the Bill and Melinda Gates Foundation.

In the study headed by Dr. John R. Carlson at Yale, researchers transferred 72 Anopheles odor receptor genes, one by one, into mutant fruit flies that lacked odor receptors in certain nerve cells. The resulting flies each carried a unique mosquito odor receptor in these neurons. The flies were exposed to a series of 110 scent molecules, and electrodes recorded the responses of each Anopheles receptor.

As reported in the advance online edition of Nature on February 3, 2010, the researchers identified several Anopheles receptors that responded strongly to components of human odor. While most receptors reacted to many different scents, some seemed specialized and responded to just one or a few odor molecules.

Most of the tested odors likewise activated many different receptors. But some biologically important scents—like those that trigger egg-laying or that are found in human sweat and breath—strongly activated just a few specific receptors. The study also showed that some molecules, including 2 found in human sweat, generated relatively long receptor responses, but others led to briefer activations.

The second study, led Dr. Laurence Zwiebel at Vanderbilt, inserted the same 72 Anopheles receptor genes into frog eggs, using a technique previously developed to study the scent receptors of moths and honeybees. Within a few days, each egg's surface became dotted with a unique mosquito odor receptor. Receptors that respond to an odorant cause a reaction within the egg that can be measured. As reported on February 16, 2010, in the early online edition of the Proceedings of the National Academy of Sciences, exposing the eggs to the same panel of 110 odor molecules produced results similar to those of the fruit fly study.

"We're now screening for compounds that interact with these receptors," Carlson says. “Compounds that jam these receptors could impair the ability of mosquitoes to find us. Compounds that excite some of these receptors could help lure mosquitoes into traps or repel them. The world desperately needs new ways of controlling these mosquitoes."

—by Vicki Contie

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