NIAID Now | June 11, 2019
A weapon made from spider toxin destroys blood-sucking enemies from the inside and helps save people from disease and death. It sounds like the plot of a superhero movie, but it’s actually a new way to combat malaria. NIAID-funded researchers who developed a genetically modified mosquito-killing fungus and tested it in the West African nation of Burkina Faso have shown that it even works against mosquitoes that have become resistant to chemical insecticides.
Most of the 435,000 annual deaths from malaria occur in African countries and those who succumb are typically very young children or pregnant women. The mosquitoes that spread malaria-causing parasites are kept in check mainly by insecticide-impregnated bed nets and indoor spraying. However, mosquitoes have developed resistance to chemical insecticides and the insecticides may harm beneficial insects or cause other damage because their effects are non-specific.
Several years ago, NIAID grantee Raymond St. Leger, Ph.D., and colleagues including Ph.D. candidate Brian Lovett at the University of Maryland Department of Entomology, began laboratory studies on Metarhizium pingshaense, a fungus that naturally infects and kills mosquitoes, but does not infect people, other mammals or birds. The team amped up the killing power of Metarhizium by adding a gene that codes for a toxin made by the Australian Blue Mountains funnel-web spider. They also included a genetic “switch” from the fungus that turns the toxin gene on only after fungal spores have penetrated the mosquito exoskeleton. The modified fungus killed mosquitoes faster than wild-type fungus, suggesting that it might be capable of killing off the insects before they could spread malaria. The previous lab-based studies showed that the modified fungus killed only mosquitoes and did not harm non-target insects, like honeybees.
In a study published recently in Science, the investigators took the modified fungus out of the lab and into the field to test it in near-natural conditions. The “field” in this case was not fully outdoors, but rather was contained in a sort of mini-village built inside a domed, net-covered structure called a MosquitoSphere. NIAID funded the development of the MosquitoSphere in the malaria-endemic village of Soumousso, Burkina Faso, as a tool to study genetically modified organisms in semi-field conditions. The 6,500-square-foot space contained multiple screened-in areas with experimental huts, plants, pools of water where mosquitoes could breed, and calves that served as food sources for the adult female mosquitoes. The netting meant temperature and humidity in the experimental space represented the surrounding conditions.
The University of Maryland team collaborated with scientists from Burkina Faso’s Research Institute for Health Sciences to conduct the trial. They were aided by volunteers who collected larvae and pupae of insecticide-resistant Anopheles coluzzii mosquitoes from local water sources. These wild-caught mosquitoes matured into adults that were placed in the experimental compartments inside the MosquitoSphere. Each space had a black cloth—for the mosquitoes to rest on after blood-feeding—affixed to one wall. All the cloths were coated with sesame oil, which allowed the fungal spores to adhere. In one compartment, which served as a control, no spores were placed on the oil-coated cloth. A second space contained wild-type Metarhizium fungal spores, while the third contained the modified fungus. Populations of 1,000 male and 500 female mosquitoes were released into each space and allowed to mate.
Each day for the next 45 days (the time needed to produce two generations of mosquitoes), researchers counted the number of mosquitoes at every life stage in each contained space. In the fungus-free compartment, nearly 1,400 adult mosquitoes were collected in the second generation. In the compartment containing wild-type fungus, 455 mosquitoes were collected in the second generation—a reduction, but still numerous. From the compartment containing modified fungus, the team found 399 hatched mosquitoes in the first generation but a mere 13 adults in the second generation. Because male mosquitoes must form swarms of about 1,000 in order to breed, the fungus delivering the spider toxin essentially wiped out their capacity to reproduce and thus their ability to spread malaria. While both forms of fungus eventually killed roughly 75 percent of mosquitoes over two weeks, the genetically engineered form worked faster and killed more mosquitoes. The team repeated the experiment three times—with similar results—during the height of mosquito breeding season from June to October.
These findings have generated international excitement, but Lovett warns there is more to be done before application. “This study provides promising scientific results, but a technology cannot be developed with science alone,” he said. “From the start, we and our Burkinabe colleagues, Drs Abdoulaye Diabate and Lea Pare Toe, have worked hard on its regulatory and community engagement aspects. More work is needed to attain further regulatory approval and continued social acceptance for this biotechnology before testing it in an open-field setting. This process will take time, and the pace of development will be up to the local community and other stakeholders.”
Read more about NIAID-supported research on mosquitoes and other disease vectors.
Reference: B Lovett et al. Transgenic Metarhizium rapidly kills mosquitoes in a malaria-endemic region of Burkina Faso. Science DOI: 10.1126/science.aaw8737 (2019).