Pictured is an Anopheles mosquito infected with a strain of the Metarhizium anisopliae fungus that has been labeled with a gene for fluorescence. Image by Weiguo Fang, Univ. of Maryland.
New findings by a Univ. of Maryland-led team of scientists
indicate that a genetically engineered fungus carrying genes for a human
anti-malarial antibody or a scorpion anti-malarial toxin could be a highly
effective, specific and environmentally friendly tool for combating malaria, at
a time when the effectiveness of current pesticides against malaria mosquitoes
In a study published in Science, the researchers
also say that this general approach could be used for controlling other
devastating insect and tick bug-borne diseases, such as or dengue fever and
Lyme disease. “Though applied here to combat malaria, our transgenic
fungal approach is a very flexible one that allows design and delivery of gene
products targeted to almost any disease-carrying arthropod,” said Raymond
St. Leger, a professor of Entomology at the Univ. of Maryland.
“In this current study we show that spraying
malaria-transmitting mosquitoes with a fungus genetically altered to produce molecules
that target malaria-causing sporozoites could reduce disease transmission to
humans by at least five-fold compared to using an un-engineered fungus,”
St. Leger said.
St. Leger, his post doctoral researcher Weiguo Fang and
colleagues at the Johns Hopkins School of Public Health and the Univ. of
Westminster, London created their transgenic anti-malarial fungus, by starting
with Metarhizium anisopliae, a fungus
that naturally attacks mosquitoes, and then inserting into it genes for a human
antibody or a scorpion toxin. Both the antibody and the toxin specifically
target the malaria-causing parasite P.
falciparum. The team then compared three groups of mosquitoes all heavily
infected with the malaria parasite. In the first group were mosquitoes sprayed
with the transgenic fungus, in the second were those sprayed with an unaltered
or natural strain of the fungus, and in the third group were mosquitoes not
sprayed with any fungus.
(L-R) Fang and St. Leger in their Maryland lab. Image by Univ. of Maryland.
The research team found that compared to the other
treatments, spraying mosquitoes with the transgenic fungus significantly
reduced parasite development. The malaria-causing parasite P. falciparum was found in the salivary glands of just 25% of the
mosquitoes sprayed with the transgenic fungi, compared to 87% of those sprayed
with the wild-type strain of the fungus and to 94% of those that were not
sprayed. Even 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 the mosquitoes sprayed with the wild-type fungus.
“Now that we’ve demonstrated the effectiveness of this
approach and cleared several U.S.
regulatory hurdles for transgenic Metarhizium products, our principal aim is to
get this technology into field-testing in Africa
as soon as possible,” St. Leger said. “However, we also want to test
some additional combinations to make sure we have the optimized malaria-blocking
Noting that the Univ.
of Maryland has pioneered the science
and practice of creating transgenic fungi, St Leger said that he and colleagues
and at partnering institutions are already working to create genetically
engineered fungi that can be used to reduce transmission of other illnesses,
like Lyme disease and sleeping sickness. In related work, they are employing
genes encoding highly specific toxins to produce hypervirulent pathogens that
can control pests like locusts, bed bugs and stink bugs.
“Insects are a critical part of the natural diversity
and the health of our environment, but our interactions with them aren’t always
to our benefit,” said St. Leger, who is widely recognized for research
that employs insects and their pathogens as models for understanding how
pathogens in general cause disease, adapt and evolve, and in the application of
that understanding to the creation of new methods for safely reducing crop
destruction, disease transmission and other damaging insect impacts.
The Malaria Challenge
Infection by malaria-causing parasites results in approximately
240 million cases around the globe annually, and causes more than 850,000
deaths each year, mostly children, according to the World Health Organization.
Most of these cases occur in sub-Saharan Africa,
but the disease is present in 108 countries in regions around the world.
Treating bed nets and indoor walls with insecticides is the main prevention
strategy in developing countries, but mosquitoes are slowly becoming resistant
to these insecticides, rendering them ineffective.
This stink bug has been infected with a fungi. St. Leger and his team also are creating transgenic fungi designed to control stink bugs, bed bugs, locusts and other pests. Image by Weiguo Fang, Univ. of Maryland.
“Malaria prevention strategies can greatly reduce the
worldwide burden of this disease, but, as mosquitoes continue to acquire
resistance to currently used methods, new and innovative ways to prevent
malaria will be needed, experts say.
One such strategy is killing Anopheles mosquitoes by
spraying them with the pathogenic fungus M.
anisopliae. Previous studies by African, Dutch, and British scientists have
found that this method nearly eliminates disease transmission but only when
mosquitoes are sprayed soon after being infected by the malaria parasite. The
difficulties with this strategy are that it requires high coverage with fungal
biopesticides to ensure early infection, and is not sustainable in the long
term. If spraying mosquitoes with M.
anisopliae kills them before they have a chance to reproduce and pass on
their susceptibility, mosquitoes that are resistant to the fungus will soon
become predominant and the spray will no longer be effective.
The approach developed by St. Leger and his colleagues
avoids these problems because their engineered strains selectively target the
parasite within the mosquito, and allow the fungus to combat malaria when
applied to mosquitoes that already have advanced malaria infections. In
addition “Our engineered strains slow speed of kill enable mosquitoes to
achieve part of their reproductive output, and so reduces selection pressure
for resistance to the biopesticide,” St. Leger said. “Mosquitoes have
an incredible ability to evolve and adapt so there may be no permanent fix.
However, our current transgenic combination could translate into additional
decades of effective use of fungi as an anti-malarial biopesticide.”
The National Institute of Allergy and Infectious Diseases
(NIAID), part of the National Institutes of Health, funded this research.