Lab-engineered organism fights malaria

Fungus attacks not just mosquitoes, but parasites inside them

Malaria’s new worst enemy may be a fungus.

A fungus? Try stealth assassin. Strains of a common fungus engineered by a U.S.-British team can eliminate more than 90 percent of malaria parasites deep within the insects that carry them, the team reports February 25 in Science.

Malaria is caused by several species of single-celled organisms known as protozoans. But the disease is really an insect’s game. Mosquitoes are malaria’s taxi service, shuttling pathogens from person to person and town to town. Good malaria control, then, is about good insect control, says Andrew Read, an evolutionary biologist at Penn State University in University Park, Pa.

The flow of pesticides to malaria-prone regions like Africa and Asia, however, has put mosquitoes under big pressure to evolve resistance to insect-killing chemicals. “These things work until the mosquito becomes resistant, and then you’re in trouble,” says Read, who was not involved in this study.

The tiny fungus Metarhizium anisopliae could present a solution. This fungus naturally infects mosquitoes but, unlike pesticides, takes days to kill them. That doesn’t sound like a good thing — more time means the mosquitoes have longer to mate, which means more mosquitoes. But the more bugs mate, the less reason they have to evolve resistance, since they are already able to pass along their genes. The fungus seems to walk a fine line between promoting resistance by killing insects too early, and allowing too many chances to spread the disease by killing them too late.

Yet Raymond St. Leger and his colleagues didn’t want to just kill insects. The team added a few new genes to the fungal DNA, turning M. anisopliae into a drug-producing factory. First, the modified fungus bores a hole into the mosquito. Inside, the added genes turn on and, depending on the fungal strain used, generate a host of malaria-killing chemicals, from scorpion toxins to proteins from the human immune system. The chemicals are bad for parasites but don’t do any extra harm to mosquitoes, says St. Leger, an entomologist at the University of Maryland in College Park, Md.

“They’re catching the malaria as it swims from the insect gut to the insect salivary gland,” he says. One fungal strain cured malarial infections in about 75 percent of dosed insects, and killed more than 90 percent of the pathogens in the rest.

No one’s sure how many malaria parasites it takes to actually launch the disease, says Adriana Costero-Saint Denis, a scientist with the National Institute of Allergy and Infectious Diseases, which funded the study. Rigorous testing will show whether St. Leger’s super-fungi work under real-world conditions. “Even though this discovery is extremely exciting, it’s still a long way from being a tool in the field,” she says.

Genetic engineering involves a suite of regulatory issues and inevitably public critics, says Tom Miller, an entomologist currently on a fellowship in Washington, D.C., with the U.S. State Department. The modified fungi are safe but not miracle cures, adds Miller, who is working with St. Leger on a separate study. He’d like to see such tools used alongside new and better medicines.

St. Leger sees a lot of potential for lab-engineered assassin fungi — which scientists can mix into house paint or weave into mosquito nets. His newest efforts focus on killing Lyme disease inside tick innards. “We’re not limited to what we already have,” he says, “or what even nature has.”

‘SHROOMED In a new approach to malaria control, killer lab-built fungi poison infect mosquitos and poison the malaria parasites living inside the insects. The mosquitos die a few days later. Weiguo Fang

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