July 15, 2010 | 7
An estimated one million people die each year from malaria, a parasitic infection transmitted by mosquitoes. Current control strategies involve blasting the bugs with insecticides, or using drugs to kill the parasite once it infects humans. Unfortunately, these methods are becoming less effective as both pests evolve ways to resist the toxic treatments, so new methods to prevent malaria are sorely needed.In recent years scientists have tinkered with the insect’s genes with hopes of developing modified mosquitoes incapable of transmitting the parasite. Although promising, these efforts produced mosquitoes with only reduced parasite transmission. Now, researchers led by University of Arizona entomology professor Michael Riehle report that they have developed a transgenic mosquito that is completely immune to infection by Plasmodium falciparum, the primary malaria-causing parasite in humans. The researchers hope that their findings will one day be used as part of a new strategy to combat malaria.
For malaria to spread, a female Anopheles mosquito must first ingest the parasite by dining on an infected person. Once inside the mosquito, the parasite undergoes an approximately two-week maturation process, traveling from the mosquito gut to the salivary gland where it is then ready to be spread to other human hosts.
Fortunately for humans, mosquitoes in malaria-endemic regions rarely survive more than two weeks. Therefore, the researchers sought to investigate ways to shorten the mosquito’s lifespan because "even a modest reduction in lifespan could significantly impact parasite transmission," the authors wrote in their paper, published online July 15 in PLoS Pathogens.
The researchers used information that has been learned by studying longevity and immunity in other model organisms, particularly fruit flies and nematodes, to target a gene in the mosquito suspected to control mosquito lifespan and regulate its resistance to infection. The team engineered the mosquitoes to express high levels of the active form of a protein known as Akt, and found that the transgenic mosquitoes not only had a shorter lifespan—approximately 20 percent shorter than controls—parasite infection was completely blocked.
"We were surprised how well this works," Riehle said, in a prepared statement. "We were just hoping to see some effect on the mosquitoes’ growth rate, lifespan or their susceptibility to the parasite, but it was great to see that our construct blocked the infection process completely."
This is an important first step because it only takes one parasite to make a mosquito infective—if even a single parasite survives, it can go on to produce thousands of progeny, Riehle says. He adds that his team would like to figure out how the parasites are being killed because that information could be used to make even more resistant mosquitoes.
In order for any transgenic mosquito to be truly effective against malaria, however, the transgenic bugs will have to out-compete wild mosquitoes and eventually displace them, a significant challenge that Riehle acknowledges and hopes to tackle in the future. Until that happens, Riehle’s genetically modified mosquitoes are safely secured in his lab.
Image of a mosquito larva with a red fluorescent marker indicating that it has the genetic modification that makes it immune to the malaria parasite, courtesy of M. Riehle, University of Arizona