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Transgenic Fungi Being Developed to Fight Malaria

(Beyond Pesticides, March 1, 2011) As insect resistance to pesticides steadily increases, and the underlying conditions of poverty, poor water management, and indecent living conditions contribute to the spread of malaria, the search for silver bullet solutions escalates. Researchers are exploring genetic engineering as the next frontier for a product-based approach to fighting malaria, which annually kills nearly one million people worldwide. While releasing genetically engineered organisms into the environment raises serious concerns that must be fully studied, some in the public health community believe this could help slow the spread of malaria as part of an integrated campaign. At the same time, the long-term underlying causes that support the spread of malaria must be addressed.

The new research indicates that a genetically engineered fungus carrying genes for a human anti-malarial antibody or a scorpion anti-malarial toxin could be an effective tool for combating malaria, at a time when the effectiveness of current pesticides against malaria mosquitoes is declining. 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, PhD, a professor of Entomology at the University of Maryland. The study, “Development of Transgenic Fungi That Kill Human Malaria Parasites in Mosquitoes,” is published in the February 2011 in the journal Science.

University of Maryland researchers with colleagues at the Johns Hopkins School of Public Health and the University 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.

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 percent of the mosquitoes sprayed with the transgenic fungi, compared to 87 percent of those sprayed with the wild-type strain of the fungus and to 94 percent of those that were not sprayed. Even in the 25 percent of mosquitoes that still had parasites after being sprayed with the transgenic fungi, parasite numbers were reduced by over 95 percent compared to the mosquitoes sprayed with the wild-type fungus.

According to the U.S. Centers for Disease Control and Prevention (CDC), there are over 125 mosquito species with documented resistance to one or more insecticides. In a podcast interview with Science magazine, Dr. St. Leger explains why his research team believes this technology would result in less resistance than that of chemical insecticides:

The fungus isn’t interested in killing insects quickly. It wants to live inside the insect, it wants to grow inside the insect, and then it wants to produce lots of spores on the body of the insect. So, the fungus did not evolve to kill an insect quickly. It’s not to its benefit to kill the insect quickly. Now, that’s okay as long as the mosquito becomes infected with the fungus and with the malaria at about the same time. It’ll take a couple of weeks for the mosquito to become infectious with malaria, and in that time, the fungus will kill the mosquito, but that means you need to get a big dose of fungus out there in the field to help insure early infection by the fungus of the mosquito. So, that’s a problem. Now, we could engineer the fungus to kill the insect really quickly. We could put a gene encoding a scorpion toxin or a spider toxin, which is insecticidal, and that will kill the mosquito really quickly. But if we were to do that, we would very quickly start selecting for the mosquito to become resistant to the fungus, just like it’s become resistant toward the chemical insecticides, and lots of other things we’ve tried against the mosquitoes. So we tried a different tack: a fungus which will kill slowly, so it won’t put a lot of extra selective pressure on the mosquito. The mosquito can still breed somewhat, but now our fungus has genes specifically targeting the malaria, so that the mosquito is still flying around, but this fungus will penetrate into the insect, and it will kill the malaria inside the insects.

Malaria is a mosquito-borne infectious disease of humans caused by eukaryotic protists of the genus Plasmodium. It is widespread in tropical and subtropical regions, including much of Subsaharan Africa, Asia and the Americas. The disease results from the multiplication of malaria parasites within red blood cells, causing symptoms that typically include fever and headache, in severe cases progressing to coma, and death.

There are concerns by some that releasing a genetically modified organism into the environment could have negative unintended consequences. When asked about the potential hazards of this type of technology, Dr. St. Leger said this in his interview with Science:

Well, it’s hard to see any possible tangible effect this is going to have. We’re talking in our first field trials about using the fungus expressing the human antibody. Now, this antibody only recognizes the human malaria strain. It doesn’t even recognize chicken malaria or mouse malaria, so it’s highly specific. It wouldn’t affect anything the fungus does against any other insect if it doesn’t change the host range, it doesn’t change the virulence of the fungus. All it does is produce a protein which specifically interacts with human malaria. So, it’s hard to see any potential for impact. On the other hand, this sets a precedent, and although most concerns about the use of transgenic organisms have been focused on the application of transgenics to things we use as food, rather than to anything to do with human health, we still are making very sure that we cover everything. We also would make absolutely sure that we have what we call the stakeholders – everyone involved in Kenya, which is probably where the trial would take place, or maybe Tanzania – that everyone would be informed, everyone in the neighborhood would be informed of exactly what we’re doing. So we’d bring everyone on board with us. But we’re not in any hurry. We want to make sure absolutely everything is covered.


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