Led by Michael Riehle, University of Arizona entomologists introduced genetic modifications in mosquitoes in a way that renders them completely immune to the parasite, a single-celled organism called Plasmodium. Someday researchers hope to replace wild mosquitoes with lab-bred populations unable to act as vectors, i.e. transmit the malaria-causing parasite.
"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," said Riehle, a professor of entomology in the UA's College of Agriculture and Life Sciences.
Riehle's team used molecular biology techniques to design a piece of genetic information capable of inserting itself into a mosquito's genome. This construct was then injected into the eggs of the mosquitoes. The emerging generation carries the altered genetic information and passes it on to future generations. For their experiments, the scientists used Anopheles stephensi, a mosquito species that is an important malaria vector throughout the Indian subcontinent.
The researchers targeted one of the many biochemical pathways inside the mosquito's cells. Specifically, they engineered a piece of genetic code acting as a molecular switch in the complex control of metabolic functions inside the cell. The genetic construct acts like a switch that is always set to "on," leading to the permanent activity of a signalling enzyme called Akt. Akt functions as a messenger molecule in several metabolic functions, including larval development, immune response and lifespan.
When Riehle and his co-workers studied the genetically modified mosquitoes after feeding them malaria-infested blood, they noticed that the Plasmodium parasites did not infect a single study animal.
Riehle said: "We were surprised how well this works. 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."
Each new malaria case starts with a bite from a vector - a mosquito belonging to the genus Anopheles. About 25 species of Anopheles are significant vectors of the disease. Only the female Anopheles mosquitoes feed on blood, which they need to produce eggs. When they bite an infected human or animal, they ingest the malaria parasite.
At this point, the modified mosquitoes exist in a highly secured lab environment with no chance of escape. Once researchers find a way to replace wild mosquito populations with lab-bred ones, breakthroughs like the one achieved by Riehle's group could pave the way toward a world in which malaria is all but history.
The study appears in the journal Public Library of Science Pathogens.