Monday, February 20, 2012

Disease-Fighting Secrets of Genetically Modified Mosquitoes

Aedes aegypti

Insects cover our planet. Filed into 750,000 different species, at any given time there are one million trillion bugs buzzing around the globe.

About 14,000 of those species are blood-feeders, meaning they drink their meals by puncturing the skin of vertebrates, including humans. Besides being a nuisance, blood-feeding insects, such as certain strains of mosquitoes, are infected with parasitic organisms that are no threat to the bugs themselves, but if transferred to humans, become toxic, or worse, lethal.

A new collection of studies from PLoS charts alternative strategies for curbing mosquito-borne diseases such as dengue and malaria using genetically modified insects. The idea is to create mosquitoes that are less infectious and pass their altered genetics to the next generation by breeding with their natural counterparts.

Even though GM insects offer potential relief from malaria and dengue, which remain untreatable, unpreventable diseases in much of the developing world, there is still a lot of skepticism, mistrust and even fear of genetically modified organisms of any sort. Careful regulation, program oversight, and public information campaigns are just as important as proving the efficacy of GM insect release.

These pictures show the different types of mosquitoes whose genetic profiles are changing in the name of science and public health.

Above:

Aedes aegypti

Aedes aegypti is a carrier mosquito for the virus that causes dengue fever in humans. Researchers discovered that by introducing Wolbachia bacterial strains into some insects, the dengue virus didn’t live as long as usual inside the mosquitoes. What’s more, because most Wolbachia strains are relatively harmless to the insects, the bacteria spread through mosquito generations, passing from mother to offspring.

A study in Zhiyong Xi’s lab at Michigan State University found that the Wolbachia bacterium stopped the dengue virus from replicating, and therefore kept it from spreading among mosquitoes. In fact, 14 days after the study started, 37.5 percent of the mosquitoes were unable to infect humans with dengue.

Another study, from Elizabeth McGraw’s lab at The University of Queensland, Australia, showed that by using a modified Wolbachia bacteria (wMelPop), the older mosquitoes -- the insects that typically pass dengue to humans -- had a shortened lifespan because they could no longer feed. From the age of 26 days onward, the mosquitoes with the wMelPop Wolbachia bacteria in their bodies started drinking significantly less blood than their uninfected counterparts.


Aedes albopictus

Aedes albopictus

The Asian Tiger mosquito,Aedes albopictus, can carry diseases including dengue and chikungunya. Compared to its genetic relative A. aegypti, this mosquito is typically less likely to house a virus. Since A. albopictus carries less risk of infection, the latest advances in genetic engineering seemed to have been reserved for the more virulent A. aegypti.

But A. albopictus is hardier than its relatives, and travels longer distances from the equator. In the past 30 years, researchers have watched them move throughout Southeast Asia to Northern Asia to Europe to the United States. Combined with the fact that certain mutations of the chikungunya virus are now carried by these mosquitoes, more and more researchers believe finding a suitable eradication strategy is crucial.

A team of collaborators from the GM insect technology company Oxitec, Imperial College, and the University of Oxford took the first steps forward, showing they could stably deliver a transgene to A. albopictus embryos, the first genetic modification ever to be done on Asian Tiger mosquitoes.


Anopheles stephensi

Anopheles stephensi

Anopheles stephensi is a type of mosquito that can become infected by Plasmodium, parasitic protozoans that cause malaria in humans.

Two studies highlight different ways to get these mosquitoes to resist infection by Plasmodium strains. First, George Dimopoulos’s team at Johns Hopkins University created a genetically modified mosquito by triggering a certain protein (Rel2) to boost the bug’s immunity when it drank blood. The results showed that his genetic trigger worked: Rel2 increased after feeding, and there were fewer traces of Plasmodiumin the genetically modified insect’s saliva compared to the controls.

In a second study, led by Anthony James at UC Irvine, scientists showed that by introducing new genes that coded for immune system components from both mosquitoes and mice, they could create a transgenic insect that was resistant to the Plasmodium parasite.


Anopheles albimanus

Anopheles albimanus

George Dimopoulos, the researcher who showed that tweaking the Rel2 protein in A. stephensi turned on the insect’s immune system after a blood meal, has also done similar work in A. albimanus. In his proof-of-concept studies, he discovered that artificially increasing or decreasing Rel2 caused certain of the mosquitoe's immunity genes to turn on or off, respectively.

Anopheles gambiae

Anopheles gambiae

Anopheles gambiae is the most important Anopheles species for malaria in Africa.

A group led by Steven Sinkins at the University of Oxford found that simply introducing a modifiedWalbachia strain was enough to shorten the insect's lifespan, halt the development of the Plasmodiumpathogen, and activate the parts of the mosquito’s immune system that affect whether an infective parasite will live or die within the host.

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