Insecticide resistance is weakening the protective effect of bed nets against malaria.

SARAH WEISER

Fungus with a venom gene could be new mosquito killer

In the 1980s, the village of Soumousso in Burkina Faso helped launch one of the most powerful weapons against malaria: insecticide-treated bed nets, which had early field trials there and went on to save millions of lives. But as mosquitoes developed resistance to widely used insecticides, the nets lost some of their power. Now, researchers are hoping the village can help make history again by testing a new counter-measure: a genetically modified (GM) fungus that kills malaria-carrying mosquitoes. In tests in a 600-square-meter structure in Soumousso called the MosquitoSphere—built like greenhouse but with mosquito netting instead of glass—the fungus eliminated 99% of the mosquitoes within a month, scientists report in this issue of Science.

"To be able to clear insecticide-resistant mosquitoes to this level is amazing," says entomologist Marit Farenhorst of In2Care, a mosquito control company in Wageningen, the Netherlands. But Farenhorst, who was not involved in the study, emphasizes that the fungus is a long way from real-world use. Because it is genetically modified to make it more lethal, it could face steep regulatory obstacles. The fungus also has clear advantages, however: It spares insects other than mosquitoes, and because it doesn't survive long in sunlight, it's unlikely to spread outside the building interiors where it would be applied.

Fungi naturally infect a variety of insects, consuming the host's tissues in order to reproduce, and they have been used for decades to control a wide variety of crop pests. In 2005, researchers tested a fungus called Metarhizium in test huts in Tanzania and found that it killed malaria-transmitting mosquitoes. But it did so slowly, and many infected mosquitoes survived long enough to transmit malaria. It was also difficult to ensure mosquitoes picked up a lethal dose of spores.

Since then, researchers have tested dozens of different fungal strains against disease-carrying mosquitoes, but none was effective enough to pass muster. So researchers from the University of Maryland (UMD) in College Park and the Research Institute of Health Sciences & Centre Muraz in Bobo-Dioulasso, Burkina Faso, endowed a strain called M. pingshaense with a gene for a toxin isolated from spider venom that turns on when it contacts hemolymph, the insect version of blood. In the lab, the team showed its creation could kill mosquitoes faster and that just one or two spores could cause a lethal infection. "But it's hard to replicate the complexities of nature in the lab," says UMD entomologist Brian Lovett, who helped lead the study.

Burkina Faso was a promising place for a field test: Unlike many countries in Africa, it has an established system to evaluate and approve the use of GM organisms. It also has one of the highest rates of malaria in the world, and insecticide-resistant mosquitoes are widespread. For those and other reasons, the U.S. National Institutes of Health funded the MosquitoSphere, which is specifically designed to test GM organisms.

The researchers cooperated with local residents to collect insecticide-resistant larvae from shallow pools and raised them to adulthood inside the facility. After biting, the female mosquitoes prefer to rest on a dark-colored surface, so the team mixed the fungus in locally produced sesame oil and spread the oil on black cotton sheets, which they hung in the sphere's test compartments.

The team compared sheets treated with wild type fungus, the transgenic fungus, and oil without fungus. They released 500 female and 1000 male mosquitoes in each test compartment and gave the mosquitoes a calf to feed on for two nights every week. After two generations—45 days—there were as many as 2500 adult mosquitoes in the control compartment, roughly 700 in the compartment with wild type fungus, but only 13 in the compartment with the GM fungus. "It's an elegant study," Farenhorst says. However, she notes that receiving approval for a GM fungus will be time-consuming and expensive in many places, and anti-GM groups may object, as they do against malaria-resistant GM mosquitoes. "I'm not convinced that this is the way forward."

But Gerry Killeen, a malaria expert at the Ifakara Health Institute in Dar es Salaam, Tanzania, says the transgenic fungus might have an advantage over those found in nature: If it could be patented, it could be easier to turn into a product worthwhile for a company to develop and market. "The greatest barrier to new malaria control tools isn't lack of technology or imagination, it's the lack of a market," he says. And because the transgenic fungus needs so few spores to cause a lethal infection, the product could be longer-lasting and less expensive than unmodified fungi. "If this technology has the potential to reduce costs and extend product lifetime simply by being more potent," Killeen says, "then bring it on."