A team of US scientists has bioengineered the world’s first malaria-proof mosquito: they said their new genetically modified mosquito has 100 per cent immunity to the malaria parasite, rendering it incapable of spreading the disease to humans. They hope one day that wild mosquitoes will be replaced with malaria-proof strains, effectively wiping out a disease that kills 1 million people worldwide every year, most of them children.

You can read about how lead researcher Dr Michael Riehle, a professor of entomology at the University of Arizona’s College of Agriculture and Life Sciences in Tucson, and colleagues bred the new mosquito, in a study reported online on 15 July in the journal Public Library of Science Pathogens.

Riehle and colleagues are holding their genetically modified mosquitoes in a highly secure lab so they have no chance to escape while scientists work on a way to replace wild populations with lab-bred.

Other research teams have tried to bioengineer malaria-resistant mosquitoes, but this is the first time that scientists have successfully produced one that is 100 per cent malaria-proof.

Riehle, who is also a member of the University of Arizona’s BIO5 Institute, told the press that:

“If you want to effectively stop the spreading of the malaria parasite, you need mosquitoes that are no less than 100 percent resistant to it.”

“If a single parasite slips through and infects a human, the whole approach will be doomed to fail,” he added.

People contract malaria when infected female Anopheles mosquitoes bite them to to feed on their blood, which they need to produce eggs.

Around 25 species of Anopheles are significant carriers of several forms of malaria parasite, Plasmodium falciparum being the one that is most important to humans.

Once inside the mosquito’s gut, the Plasmodium cells squeeze through the midgut lining and begin a complex cycle of development that takes about 2 weeks to complete.

Most of the parasite cells don’t survive and are destroyed by the mosquito’s immune cells, but a small fraction does: these attach themselves to the outside of the midgut wall and develop brooding cells called oocysts, which 10-12 days later produce thousands of new Plasmodium cells or sporozoites.

Once hatched, the sporozoites travel to the mosquito’s salivary glands and then pass into the new host’s bloodstream when the mosquito bites them.

For their study, which was sponsored by the National Institutes of Health, Riehle and colleagues used Anopheles stephensi, a species important for spreading malaria in south Asia.

Using molecular biology techniques to alter a piece of genetic code, they targeted a biochemical pathway inside the mosquito’s cells. The pathway belongs to a signalling enzyme called Akt, and the alterted genetic code effectively causes the signal to keep the enzyme permanently active. Akt is an important messenger in various metabolic processes involved in the development of mosquito larvae, immune system response, and lifespan.

They inserted the altered genetic code into the Anopheles stephensi eggs so the adults that developed from those eggs carried the altered code in their genomes and passed it onto future generations.

The researchers found that the blood of lab animals bitten by Plasmodium-infested mosquitoes that carried two identical forms of the altered gene (ie they inherited the genetic modification from both parents), was free of the parasite: not a single study animal became infected. They also found that in those mosquitoes, not a single Plasmodium oocyst was produced.

“In homozygous mosquitoes with increased Akt signaling parasite infection was completely blocked,” they wrote, adding that the “increase in midgut-specific Akt signaling also led to an 18-20% reduction in the average mosquito lifespan”.

Riehle and colleagues concluded therefore, that “activation of Akt signaling reduced the number of infected mosquitoes, the number of malaria parasites per infected mosquito, and the duration of mosquito infectivity”.

Riehle said they were surprised at how well it worked.

“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,” he added.

Riehle said that eradication of malaria requires three elements:

“A gene that disrupts the development of the parasite inside the mosquito, a genetic technique to bring that gene into the mosquito genome and a mechanism that gives the modified mosquito an edge over the natural populations so they can displace them over time.”

He said the third element is the most challenging, which is why they decided to tackle the other two first. The benefit, as the experiment showed, is in two parts: first disrupting the Akt signalling breaks the infection cycle, and secondly, reducing the mosquito’s lifespan reduces the number of infections.

“Activation of Akt Signaling Reduces the Prevalence and Intensity of Malaria Parasite Infection and Lifespan in Anopheles stephensi Mosquitoes.”
Vanessa Corby-Harris, Anna Drexler, Laurel Watkins de Jong, Yevgeniya Antonova, Nazzy Pakpour, Rolf Ziegler, Frank Ramberg, Edwin E Lewis, Jessica M Brown, Shirley Luckhart, Michael A Riehle.
PLoS Pathogens, Published online 15 Jul 2010.

Source: University of Arizona.

Written by: Catharine Paddock, PhD