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Making Blood-Sucking Deadly

Photo: A mosquitoe on human skin
If a mosquito finds enough victims
to bite and avoids being squashed,
it can live as long as three weeks.
During that time, it may lay up to
five clutches of more than 100 eggs
each; © panthermedia.net /
Grischa Georgiew

The approach could be used as an additional strategy in the worldwide effort to curb mosquito-borne diseases like dengue fever, yellow fever and malaria.

When the researchers blocked a cellular process known as vesicle transport, on which the mosquitoes rely to release digestive enzymes into the gut among other functions, it caused the affected animals to die within two days of blood feeding.

"The idea behind our research is this: If we can kill the mosquito after she bites the first person, she won't be able to bite and infect a second," said Roger Miesfeld, a professor in the UA's department of chemistry and biochemistry, who led the research project. "We do this by blocking the mosquito's ability to digest its blood meal," said Miesfeld, also a member of the UA's BIO5 Institute.

"During a blood meal, a mosquito ingests its body weight in blood. It's the equivalent of a 125-pound human consuming a twelve-gallon smoothie made from 25 pounds of hamburger meat plus a half pound of butter and two tablespoons of sugar," Miesfeld said.

His team used a technique called RNAi to specifically target genes that are required for the digestion process. The researchers homed in on a protein complex called COPI, which stands for coatomer protein 1. COPI consists of several subunits that together make up the envelope of the vesicles on which the cell relies for internal transport and for secretion of enzymes into the gut.

When a female mosquito takes a blood meal, the cells lining its gut secrete enzymes to break down the blood proteins. The secretion process involves packaging the enzymes in small droplets called vesicles that the cells then release into the gut.

"We thought, 'Why don't we knock out the whole process that allows the proteases to be secreted?' That's where we got this amazing result," Miesfeld said. "Not only did we eliminate her ability to secrete anything, we were surprised to find that about 90 percent of those mosquitoes died within two days after feeding on blood."

The COPI RNAi does not have an adverse effect on the female mosquitoes for 10 days – unless they decide to take a blood meal. "When she does, all hell starts breaking loose, biochemically and anatomically speaking," Miesfeld said. For this to be an effective mosquito-selective insecticide, it must not have any effect on humans.

As part of this strategy, the researchers are looking for genes that are unique to the mosquito and could serve as targets without affecting human health.


MEDICA.de; Source: University of Arizona

 
 
 

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