Photo by Neil Brake
Larry Zwiebel with a bucket of mosquitoes

Today, we know a little bit more about one of mankind's deadliest enemies, the mosquito. Scientists have taken an important step toward understanding the mosquito's sense of smell, its primary method for picking its prey.

In a joint effort reported in the Jan. 15 issue of the journal Nature , researchers at Vanderbilt and Yale universities have verified that the antennae of female Anopheles gambiae mosquitoes that prey on humans contain receptors that respond to one of the chemical compounds found in human sweat.

“This validates our hypothesis that the olfactory system of mosquitoes, and other insects, consists of an array of different receptors, each of which responds to a very narrow range of odorants,” says Laurence J. Zwiebel , associate professor of biological sciences at Vanderbilt, who participated in the study. His co-authors were Vanderbilt graduate student A. Nicole Fox along with Yale colleagues graduate student Elissa A. Halem and professor John R. Carlson.

	Photo by Neil Brake
	Nicole Fox working in the lab

Confirmation of this hypothesis means that it should be possible to identify the specific human odorants and the protein receptors that allow female mosquitoes to identify their hosts when they need blood to satisfy their reproductive needs. In addition to cataloging the human odorants that attract mosquitoes, it also will allow the researchers to go further and search for additional chemicals that either attract or repel these highly selective insects.

“Looking at attractants is only half of the picture. There is no evidence that mosquitoes find some human odorants repellent, but we're interested in exploring this,” says Zwiebel. Such discoveries might lead to new and more effective repellants that could play a major role in reducing the death toll from diseases spread by mosquitoes, including malaria, encephalitis, West Nile , dengue, hemorrhagic and yellow fevers.

Previous studies have shown that human sweat contains about 350 different aromatic compounds, but not much research has been done on them. For example, researchers do not know much about the individual variations in these odorants, not even how greatly the odorants of men and women differ. However, recent data from researchers in the Netherlands suggests that mosquitoes use a blend of many odorants in targeting prey. “This is a very complex system,” Zwiebel observes.

Photo by Neil Brake

A passel of Anopheles mosquitoes

The Nature paper reports another important advance. The researchers were able to get a mosquito olfactory gene to work in Drosophila , the fruit fly that has become the “white lab rat” of genetic research. This provides the researchers with a wealth of tools that they can use to explore the nature of the mosquito's olfactory system at the genetic and molecular level.

	Courtesy of Laurence Zwiebel
	A close-up of a female Anopheles antenna, taken with a scanning electron microscope, shows several different types of olfactory bristles (sensilla). The grooved peg sensilla, labeled gp, are thought to be directly involved in choosing prey for blood meals. In addition, the mosquito uses the mechano-responsive sensilla (MR) for flight direction and the St(I) sensilla are involved in egg laying behaviors

The researchers created fruit flies with Anopheles' olfactory genes and then tested their sensitivity to different compounds found in human sweat. They identified one particular compound, 4-methylphenol, strongly activated an odorant receptor that is expressed in female mosquitoes but not in males. Previous studies had shown that the production of this protein is suppressed in female mosquitoes immediately following a blood meal when they are no longer responsive to human odors. The new finding strengthens the argument that female Anopheles use 4-methylphenol to seek out hosts.

The fact that the mosquito gene works properly in the fruit fly has another significant ramification. It means that the fundamental nature of the olfactory system in other insects must be extremely similar to that of the mosquito. “As a result, our research should have a direct bearing not only on the mosquito, but also on other insects that carry disease and act as agricultural pests,” Zwiebel says.

Nature article: "Olfaction: Mosquito receptor for human-sweat odorant;" Jan
15, 2004

Yale News Release: Yale Scientists Identify How Chemical in Human Sweat
Attracts Mosquitoes

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