The Repellence Cocktail: Mosquito Sense of Smell Reveals More Mysteries

Walter Leal
In a study published in iScience, Distinguished Professor Walter Leal and his colleagues showed that the southern house mosquito possesses a single odorant receptor that exhibits both inhibitory and excitatory responses. David Slipher/UC Davis

When nibbling mosquitoes cause irritation, the sensible move is to grab mosquito repellent. Distinguished Professor Walter Leal, Department of Molecular and Cellular Biology, likes to remind his students of this. But if they’re stepping outside for only a short period of time during the buggy Davis summers, Leal will offer a natural repellent like methyl salicylate, otherwise known as wintergreen oil.

While we know certain plant-derived compounds act as insect repellents, much of the molecular science behind insect olfaction remains a mystery. Typically, it’s believed that for a mosquito olfactory neuron to be functional it requires separate odorant receptors and co-receptors that excite and inhibit odorant signals. But in a study published in iScience, UC Davis researchers showed that the southern house mosquito possesses a single odorant receptor that exhibits both inhibitory and excitatory responses.

“We found that these receptors elicit excitatory responses to some plant compounds but inhibit signals from other plant compounds,” said Leal. “That’s the dual functionality.”

The research has exposed further layers of complexity in the mosquito olfactory system. 

“It’s a very interesting thing and it really happened accidentally,” said Leal.   


From frog eggs to fruit flies

Pingxi Xu, a project scientist in Leal’s lab, was first to stumble upon the duality of the odorant receptor CquiOR32, which is found in the southern house mosquito (Culex quinquefasciatus). In the lab, Xu tested the receptor against various chemical compounds, some known attractors and others repellents of mosquitoes. First, he tested the receptor by injecting it into the oocytes of the African-clawed frog (Xenopus laevis), a common model organism.

“All the machinery that you need for a receptor already exists in the egg,” said Leal, explaining why they use the system in their experiments.   

Southern house mosquito
This illustration depicts a typical adult Culex quinquefasciatus mosquito. Public Health Image Library

Compounds like methyl salicylate (wintergreen oil) elicited expected excitatory responses from the receptor. But compounds like eucalyptol, found in eucalyptus trees, elicited an inverse response from the receptor, acting like an inhibitor. Surprised by the duality of the responses, the team decided to further test the system by jumping model organisms.

Using Drosophila melanogaster (popularly known as the fruit fly or vinegar fly), the team created transgenic flies with the CquiOR32 receptor. They then tested methyl salicylate, eucalyptol and mixtures of the two on the flies and recorded electroantennogram (EAG) responses, which are used to test an insect’s antennae response to odors. When the compounds were tested individually, the flies’ antennae responded similarly to the receptors in the oocytes. The chemical mixture elicited similar receptor responses to that of eucalyptol, suggesting that eucalyptol dampened the repellent effect of methyl salicylate.

Leal and his lab
The research has exposed further layers of complexity in the mosquito olfactory system, which Leal and his colleagues plan to study further. David Slipher/UC Davis

A whiff of the mosquito sensory system

For further confirmation of their findings, the team tested the chemicals on mosquitoes. As expected, methyl salicylate repelled mosquitoes but when mixed with eucalyptol, its effectiveness decreased significantly, as was shown in the transgenic flies.

According to Leal, the study has unveiled new molecular mechanisms behind insect olfaction.

“We knew for many years that there are chemicals that inhibit signals for insect olfaction,” he said, “but no one knew how this thing works properly.”

Hopefully, these findings will lay the foundation for the discovery or the design of environmentally friendly compounds that can keep mosquitoes at bay,” added Leal.        

The research was supported by the National Institute of Allery and Infectious Diseases, part of the National Institutes of Health.   

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Leal and Pingxi Xu
Leal and Pingxi Xu test insect antennae for olfactory responses to various chemical scents. David Slipher/UC Davis