New findings by a University of Maryland-led team of scientists indicate that a genetically engineered fungus carrying genes for a human anti-malarial antibody or a scorpion anti-malarial toxin could be a highly effective, specific and environmentally friendly tool for combating malaria, at a time when the effectiveness of current pesticides against malaria mosquitoes is declining.
In a study published in the February 25 issue of the journal Science, 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, a professor of Entomology at the University of Maryland.
"In this current study we show that spraying malaria-transmitting mosquitoes with a fungus genetically altered to produce molecules that target malaria-causing sporozoites could reduce disease transmission to humans by at least five-fold compared to using an un-engineered fungus," St. Leger said.
St. Leger, his post doctoral researcher Weiguo Fang and 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.
"Now that we've demonstrated the effectiveness of this approach and cleared several U.S. regulatory hurdles for transgenic Metarhizium products, our principal aim is to get this technology into field-testing in Africa as soon as possible," St. Leger said. "However, we also want to test some additional combinations to make sure we have the optimized malaria-blocking pathogen."