Proteins show promise for mosquito control

Main Category: Cholesterol
Article Date: 11 Sep 2004 - 8:00 PDT

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Mosquito abatement usually means one thing: blasting the pesky critters with pesticides. Those pesticides, although highly effective, can impair other organisms in the environment. Que Lan, insect physiologist at the University of Wisconsin-Madison, and her colleagues in the entomology department are working on a new, more targeted approach to mosquito control: inhibiting their ability to metabolize cholesterol.

Cholesterol, the sticky substance that accumulates on the lining of human arteries, is an important component of cell membranes in vertebrates and invertebrates. In mosquitoes, it is vital for growth, development and egg production.

Unlike humans, mosquitoes cannot synthesize cholesterol. They must obtain it from decomposed plants they eat while in their larval stage, living in shallow waters. Plants make phytosterol, which is converted to cholesterol in the mosquito's gut.

Using the yellow fever mosquito, Aedes aegypti, Lan and her research colleagues discovered that a sterol-carrying protein, AeSCP-2, is the vehicle that transports cholesterol in mosquito cells. Cholesterol is hydrophobic. In order to transport it in a liquid medium, such as blood or cell fluids, organisms must have a way to shield it from the watery environment through which it moves. That shield is typically a carrier protein, such as SCP-2.

Lan and her colleagues reasoned that if they could block the carrier protein, it would disrupt the uptake of cholesterol by the mosquito. Screening what she calls "a small chemical library of 16,000 compounds," Lan and her team found 57 compounds that inhibited the cholesterol-binding capacity of SCP-2.

The top five most viable inhibitor compounds were then tested on mosquito larvae, producing promising results--the larvae died. The results were dose-dependent; that is, at higher concentrations, larger numbers of larvae died. Still, the concentrations were very small, Lan says, in the range of 10 parts per million.

Lan has a somewhat personal vendetta against disease-carrying mosquitoes. Growing up in China, she contracted malaria when she was 13. A school teacher recognized her symptoms and encouraged her to see a physician. "I was drenched in sweat and pale as paper," Lan recalls. Interestingly, her father had malaria when he was a teenager. "That's 50 percent of my family," she says.

"Control is urgent," Lan says. "Mosquito-borne illnesses are endemic in parts of China. Malaria is a big problem in south-central China. South of the Yangtze River the infant mortality rate is high, especially in homes without screens on the windows."

Although Lan grew up in Wuhan, a bustling city of 7 million, there were rice fields nearby. "It is a land of 10,000 lakes," she says, where rice is a major crop and the weather is hot and humid, perfect for mosquito breeding.

Worldwide, mosquitoes are notorious for spreading not only malaria, but also dengue fever (so painful it's commonly called "break bone fever"), several forms of encephalitis, yellow fever, and West Nile virus. And the numbers are increasing. The World Health Organization estimates that there are 300 million cases of mosquito-borne diseases annually. Malaria is the biggest killer, claiming a million lives a year.

The two main approaches to future mosquito control, as Lan sees it, are genetic and chemical. In the genetic approach, she says, researchers are working on ways to modify the malaria mosquito so that it cannot transmit disease, but it can still take a blood meal. The problem with that approach, she says, is that there are many uncertainties about releasing genetically modified organisms into the environment.

Lan believes that a more fine-tuned chemical approach is more practical: only one compound is selected, it works for a short period, and it targets a single insect. "People might ask, 'Why do we need more pesticides?'" Lan says. The answer is twofold: resistance and the effect on non-target species. "I believe you should develop smart pesticides to only kill the mosquitoes," Lan says. "We don't want to go down the same road as DDT."

To that end, her team is testing the most promising handful of SCP inhibitor compounds on a variety of insect and vertebrate species. So far three of the five compounds tested were not toxic to mouse cells and the other two were only slightly toxic. They will also test the compounds on other pest species, including flies, roaches and termites.

Environmental and degradation tests have yet to be performed. "We want a specific target with low residue time- two to three weeks and it should be degraded," Lan says.

Lan and her team have patented the gene and the methods for screening the compounds. It will take a year to screen another 20,000 chemicals. After that, they will be looking for companies to develop the compounds into chemical inhibitors for widespread mosquito control.

"Four years ago (when Lan joined the faculty of UW-Madison) I couldn't imagine having five viable compounds in hand," Lan says. "This is the first example of looking at target proteins for pest management. No one has done this with insects."

Contact: Que Lan
qlan@entomology.wisc.edu
608-263-7924
University of Wisconsin-Madison