Genetically modified fungi kill malaria-causing parasites in mosquitoes

Spraying malaria-transmitting mosquitoes with a genetically modified fungus can kill the malaria parasite without harming the mosquito, potentially reducing malaria transmission to humans, according to a new study published in the journal Science. Funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, the study was led by Raymond J. St. Leger, Ph.D., of the University of Maryland, College Park.

An estimated 225 million malaria cases occur worldwide annually, resulting in about 781,000 deaths each year, according to the World Health Organisation. Although the disease is present in 106 countries around the world, most cases occur in sub-Saharan Africa. Treating bed nets and indoor walls with insecticides is the main prevention strategy in developing countries, but the Anopheles mosquitoes that transmit malaria are slowly becoming resistant to these insecticides, rendering them less effective.

'Because mosquitoes increasingly are evolving to evade the malaria control methods currently in use, NIAID-supported scientists are testing new, innovative ways to prevent malaria that we hope can be developed into tools that will be effective for years to come,' says NIAID Director Anthony S. Fauci, M.D.

One of these new strategies is killing Anopheles mosquitoes by spraying them with the naturally occurring fungus, Metarhizium anisopliae. Previous studies have found that this method nearly eliminates disease transmission when mosquitoes are sprayed soon after acquiring the malaria parasite. However, this strategy is not sustainable in the long term. If treating mosquitoes with the fungus kills them before they have a chance to reproduce and pass on their susceptibility to the spray, mosquitoes resistant to the fungus, which would reproduce normally, will soon become predominant and the spray will no longer be effective.

Because of this, Dr St. Leger and colleagues tried a more focused approach. Rather than developing fungi that rapidly kill the mosquito, they genetically modified M. anisopliae to block the development of the malaria parasite in the mosquito.

Eleven days after feeding on blood infected by the malaria parasite, mosquitoes were divided into three groups and either sprayed with naturally occurring M. anisopliae fungi, sprayed with genetically modified M. anisopliae fungi or not sprayed at all. Two weeks after exposing the mosquitoes to the malaria parasite, the researchers looked for the parasite on the salivary glands of mosquitoes in each of the three groups.

Compared with the other treatments, the modified M. anisopliae significantly reduced parasite development. The malaria parasite was found on the salivary glands of just 25 percent of the mosquitoes sprayed with the transgenic fungi, compared with 87 percent of those sprayed with the naturally occurring strain and 94 percent of unsprayed mosquitoes. The transgenic strain also reduced the density of parasites on the mosquitoes' salivary glands by more than 95 percent compared with the unmodified strain.

'The genes added to the transgenic fungi prevent the parasite from binding to the salivary glands of mosquitoes, so when a mosquito bites a human, the parasite is not transmitted,' explains Adriana Costero-Saint Denis, Ph.D., of NIAID's Vector Biology Program.

The researchers then used a model to estimate how well each fungus strain would reduce malaria transmission, and found that compared with the wild-type strain, the transgenic strain could reduce transmission to humans by fivefold, if not more.

'Our principal aim now is to get this technology into the field,' says Dr St. Leger. 'We also would like to test some additional fungal variants to make sure we have the optimised malaria-blocking pathogen,' he adds. Although they do not expect this technology to affect the environment any differently than the wild-type strain, the study authors plan to test ways to contain the transgenic fungi in the field.