Fungus fights malaria?

Researchers have engineered transgenic fungi that drill into mosquitoes and kill the malaria parasite inside -- the first tool of its kind -- a February 25, 2011 study in Science reported.Used in conjunction with traditional insecticide methods against mosquitoes, experts say this bioinsecticide has the potential to greatly improve malaria eradication efforts.

Mosquito infected with pathogenic fungus Metarhizium
Image: Courtesy of Raymond St. Leger

"This is a great example of trying to be innovative and use novel ways to look at this problem," said linkurl:Matt Thomas,;http://ento.psu.edu/directory/mbt13 a disease ecologist at Penn State who was not involved in the research. "It's a move outside the existing insecticide paradigm, which has dominated parasite and vector control for 40-50 years."Malaria is responsible for the deaths of nearly 1 million people each year, most of them children living in sub-Saharan Africa. Because the parasite that causes the disease, Plasmodium falciparum, is transmitted by a mosquito vector, scientists have historically tried to control the infection by killing the mosquitoes with insecticides. But this approach has caused the rapid evolution of insecticide-resistant mosquitoes, lessening the effects of current control tactics. "It was inevitable," said paper author linkurl:Raymond St. Leger,;http://entomology.umd.edu/directory/raymondjohnstleger a biochemist and pathologist at the University of Maryland, College Park. "We are running out of chemistries we can use. We need to find new procedures."One potential tool for the job is the parasitic fungus Metarhizium anisopliae, whose spores germinate when they land on a mosquito host, drilling into the insect's cuticle and killing it after a few days. While inside the mosquito, however, it "can be made to secrete all kinds of interesting things," said linkurl:Andrew Read,;http://ento.psu.edu/directory/afr3 an evolutionary geneticist specializing in infectious disease at Penn State, who did not participate in the study. St. Leger and his colleagues engineered the fungus to express any of three different genes that could potentially control the transmission of the malaria parasite: a gene that blocks the parasite's access to the mosquito's saliva, where it could be passed on to its next blood meal; a human anti-malaria antibody; and an antimicrobial from scorpion venom. Elegantly, these genes are only activated once the fungus hits the hemolymph of the mosquito, where the malaria parasite circulates. Individually, these genes reduced Plasmodium sporozoite counts by 71, 85 and 90 percent, respectively, when sprayed onto mosquitoes with advanced malarial infections (11 days after feeding on parasite-infected blood). Combining the scorpion antimicrobial with the gene that blocked the saliva glands eliminated a startling 98 percent of sporozoites."It's a very exciting development," said Read. "This study shows that fungi can be made to do even more exciting things with genetic engineering."Notably, the fungus has no effect on humans, meaning it could be safely released in large-scale malaria control efforts. Plus, because the fungus is slow-acting, the mosquitoes are not likely to quickly evolve resistance against its attack. "The fungus isn't interested in a quick kill, but exploiting it and producing lots of spores," said St. Leger. This gives the mosquito time to undergo her reproductive cycle several times before death, sending her non-resistant offspring into the world. There is still the possibility, however, that the malaria parasites themselves will begin to evade the wrath of the genes engineered into the fungus, linkurl:Jacob Koella,;http://www3.imperial.ac.uk/people/j.koella an epidemiologist at Imperial College London, who was not involved in the research. "While this remains as 'evolution-proof' in terms of mosquitoes... it enhances the selection pressure on malaria." But if that happens, researchers can simply reengineer this fungus to express different types of toxins, the authors argue.Unfortunately, putting the new technique into action may not be an easy task. "There are already difficult challenges in taking forward biopesticide technology," said Thomas. "Now we're adding in the additional regulatory and ethical issues around genetically modified organisms. It's not a hurdle we should just dismiss as unimportant."W. Fang et al., "Development of Transgenic Fungi That Kill Human Malaria Parasites in Mosquitoes," Science 311: 1074-77.
**__Related stories:__*** linkurl:New mosquito identified;http://www.the-scientist.com/news/display/57974/
[3rd February 2011]*linkurl:Malaria parasites synch with host;http://www.the-scientist.com/news/display/57905/
[5th January 2011]*linkurl:Evolution, Resisted;http://www.the-scientist.com/2009/10/1/44/1/
[1st October 2009]* linkurl:Related F1000 evaluations;http://f1000.com/search/evaluations?query=plasmodium+falciparum
[24th February 2011]