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.
Mosquito infected with a strain of the Metarhizium
anisopliae fungus that has been labeled with a gene for
fluorescence. Image by Weiguo Fang, University of Maryland.
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
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
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.