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A Fungal 'Vaccine' for Malaria-Carrying Mosquitoes

24 February 2011 2:00 pm
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Hugh Sturrock

Deadly spores. Fungi that kill mosquitoes could help fight malaria.

Researchers have genetically modified a fungus so that it attacks the malaria parasite within a mosquito. They hope the fungus's spores, applied to the walls of houses or mosquito traps, could help stop the spread of the disease in an environmentally friendly way.

Fungi that attack insects are present in soils worldwide, and they are used in gardens, greenhouses, and open fields to control agricultural pests. In 2005, scientists showed that strains of two different fungi, Beauveria bassiana and Metarhizium anisopliae, could attack the mosquitoes that spread malaria. When the fungal spores come in contact with the mosquito's exoskeleton, they bore their way into the hemolymph—the insect's equivalent of blood—where they grow, ultimately killing the mosquito.

But the fungi take about 2 weeks to kill the insects. "They want to kill slowly, extracting as many nutrients as possible so they can produce more spores," says Raymond St. Leger, an entomologist at the University of Maryland, College Park. Because it takes only 12 to 14 days for the malaria parasite to mature into its infective form inside the mosquito, an insect often has time to spread the parasite before a fungal infection has killed it off, especially if the mosquito is exposed to the fungus several days after it picks up the parasite.

St. Leger and his colleagues originally created a genetically modified version of the fungus M. anisopliae that, thanks to the insertion of an insect-specific neurotoxin, kills mosquitoes more quickly. But a quick kill also has a disadvantage: It can lead to mosquitoes that are resistant to the fungus, because the resistant insects are the only ones who survive long enough to reproduce.

Now St. Leger and his colleagues have engineered strains of M. anisopliae to block the malaria parasite from developing inside the infected mosquito. Online today in Science, they describe inserting different combinations of three different genes into the fungus to block the malaria parasite from entering the mosquito's salivary glands. (Parasites from the salivary glands infect new hosts when an infected mosquito bites a new victim.) One gene codes for a peptide—a short piece of a protein—called SM1 that resembles the parasite protein the parasite uses to enter the salivary glands. The copies of SM1 produced by the fungus block the parasite's way in. Another added gene codes for part of a human antibody that binds to the parasites and causes them to clump together. A third is an antimicrobial protein called scorpine—it was found in scorpions—that kills the malaria parasite.

When the researchers sprayed spores of the genetically modified fungus strains onto mosquitoes in the lab, the spores did not kill the insects faster than the normal fungus did. But they did significantly reduce the number of parasites in the mosquitoes' salivary glands: Six days after receiving spores of the genetically modified strains, the mosquitoes had 98% fewer parasites in their salivary glands than did those treated with normal fungus.

And the genetically modified fungus acts quickly. After giving mosquitoes a malaria-infected blood meal, the researchers waited 11 days before spraying some with normal fungal spores and others with the enhanced spores. Two days later, 86% of fungus-free mosquitoes could transmit malaria, as could 72% of the insects infected with normal fungus, but only 20% of the mosquitoes exposed to the transgenic fungus could do so.

The results are impressive, says Marit Farenhorst, who studies insect-attacking fungi at In2Care, a start-up company in Wageningen, the Netherlands. "In case you are a little bit late in getting the mosquito infected in field, you can still be in time to affect the transmission of malaria," she says. "It's kind of like vaccinating the mosquito." The main drawback of the approach, says Farenhorst, is that fungal spores survive only a few months when applied to walls or other surfaces. It's currently impractical and expensive to have to keep reapplying spores. But several teams are working on better ways to apply the spores and keep them alive, she says.

Although St. Leger acknowledges that widespread suspicion of genetically modified organisms might make it more difficult to persuade people to apply the fungus in their houses, he says the approach is extremely low risk: The fungus strain that the scientists modified infects only mosquitoes, the genes they inserted only recognize human malaria, and the genes are only turned on once the fungus is inside the mosquito. None of the genes give the fungus a survival advantage over the wild strains that are common in soils, he says. Still, St. Leger says, completing relevant safety tests will take several years.

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