NIH Research Matters
March 7, 2011
Fungi Developed to Fight Malaria in Mosquitoes
A genetically engineered fungus could be a highly effective tool for preventing malaria transmission. The advance might offer a new line of defense in combating a disease that affects nearly 300 million people worldwide.
Malaria is transmitted by the bite of a mosquito infected with a single-cell parasite called Plasmodium. It is one of the most common infectious diseases in the world, with over 780,000 deaths worldwide each year, mostly in young children in Sub-Saharan Africa. Treating bed nets and indoor walls with insecticides is the main prevention strategy in developing countries, but the mosquitoes that transmit malaria are slowly becoming resistant to these chemicals.
A recently developed strategy is to use Metarhizium anisopliae, a fungus that naturally attacks mosquitoes, as a mosquito-specific "biopesticide." Previous studies have shown that this method is effective in killing mosquitoes. However, the mosquitoes must acquire the fungus soon after becoming infected with the malaria parasite. Another problem is that a fungus that kills mosquitoes could rapidly lead to mosquito resistance.
An NIH-funded team led by Dr. Raymond J. St. Leger of the University of Maryland tried a more focused approach. Rather than developing fungi that rapidly kill the mosquito, they genetically modified the fungus to block Plasmodium development inside the mosquito.
The transgenic fungi produce small molecules after invading a mosquito. Among the molecules the researchers tested were a human anti-malarial antibody and a scorpion antimicrobial toxin. The researchers sprayed mosquitoes that were heavily infected with the malaria-causing parasite P. falciparum with the transgenic fungi. They then compared these mosquitoes to those sprayed with an unaltered, natural strain of the fungus or no fungus at all.
In a study published on February 25, 2011, in Science, the team reported that the transgenic fungi significantly reduced parasite development within mosquitoes. Malaria parasites were found in the salivary glands of just 25% of the mosquitoes sprayed with the most effective transgenic fungi, compared to 87% of those sprayed with the natural strain of the fungus and 94% of those that were not sprayed. In the 25% of mosquitoes that still had parasites after being sprayed with the transgenic fungi, parasite numbers were reduced by over 95% compared to mosquitoes sprayed with the unaltered fungus.
The team also found that the transgenic fungus did not significantly affect mosquito survival when compared to the wild-type fungus. This suggests that the transgenic fungi would not lead to rapid mosquito resistance when used in the field.
"Our principal aim now is to get this technology into the field," says St. Leger. "We also would like to test some additional fungal variants to make sure we have the optimized malaria-blocking pathogen."
This technique could be used to express different small molecules with different modes of action, potentially providing decades of effective use. It might also be used to combat other parasites that infect mosquitoes. The researchers don't expect the transgenic fungi to affect the environment any differently than wild-type strains, but plan to test ways to contain the transgenic fungi in the field.
- Malaria (CDC):
- Promising Malaria Drug Candidate Emerges:
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Harrison Wein, Ph.D., Editor
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NIH Research Matters is a weekly update of NIH research highlights from the Office of Communications and Public Liaison, Office of the Director, National Institutes of Health.