An experimental bacteria-derived biopesticide is highly effective in killing malaria-carrying mosquitoes, including those that have developed resistance to chemical pesticides, according to initial field tests led by researchers at the Johns Hopkins Bloomberg School of Public Health.
The biopesticide is a powder made from the dead cells of a common soil-dwelling bacterial species. The researchers showed that the biopesticide efficiently kills both ordinary and chemical-pesticide-resistant mosquitoes when included in standard baits. Even at sub-lethal doses, the biopesticide inhibits malaria transmission and makes mosquitoes more vulnerable to standard chemical pesticides. The encouraging findings from initial trials in western Africa suggest larger field tests could, if successful, one day lead to broad use of the new biopesticide in malaria-endemic parts of the world.
The study was published online December 4 in Science Advances .
"This biopesticide has a unique set of features that suggest it could be a powerful new weapon against malaria," says study senior author George Dimopoulos, PhD, deputy director of the Johns Hopkins Malaria Research Institute in the Bloomberg School's Department of Molecular Microbiology and Immunology.
Malaria, a parasitic disease spread by Anopheles mosquitoes, has long been one of the world's top killers. According to World Health Organization estimates, there are about 250 million cases and 600,000 deaths annually, mostly children under five in sub-Saharan Africa. Malaria vaccines have been developed, but are not broadly available or very efficient in preventing disease. While mosquito-killing chemical pesticides have been the most effective weapons against malaria to date, the insects have developed significant resistance to these compounds. New antimalarial tools are urgently needed.
The new biopesticide emerged from a project conducted by Dimopoulos and his team in Panama more than a decade ago. The team caught wild mosquitoes and catalogued bacterial species in their gastrointestinal tracts to see if any could affect the mosquito's ability to harbor and transmit pathogens. Ultimately, they found one, a species of Chromobacterium, that at low doses inhibits the insects' ability to transmit pathogens such as the malaria parasite and dengue virus—and at higher doses kills both adult and larval mosquitoes. This discovery suggested the bacterium could be the first biopesticide for use against disease-transmitting mosquitoes.
To avoid the complications of working with a live organism, the researchers developed a powder preparation made from dead, dried cells of the bacterium. They found that the powder retains the bacterium's mosquitocidal properties, and also has a years-long shelf life and very high heat stability. Early tests also found that the biopesticide has no evident toxic effects on mammalian cells, is readily ingested by mosquitoes when dissolved in standard mosquito baits, and—unlike chemical insecticides—does not lead to the development of genetic resistance in mosquitoes even after ten generations of mild exposure.
In the new study, the researchers tested the new biopesticide in laboratory conditions, and in "MosquitoSphere" facilities—large, net-enclosed spaces simulating village and agricultural settings—in Burkina Faso. The biopesticide killed both laboratory and wild-caught strains of Anopheles, including those with resistance to different kinds of chemical pesticides. Even when the biopesticide didn't kill the insects, it largely reversed their chemical insecticide resistance.
At the highest dose of 200 mg/ml, the biopesticide wiped out the vast majority of the mosquitoes in the MosquitoSphere facilities, and the researchers' mathematical modeling suggested that it would dramatically reduce local mosquito populations in real-world conditions.
Mosquitoes exposed to the biopesticide even at low doses were also severely impaired in their ability to seek out a host for blood meals. In the relatively few insects that succeeded in ingesting malaria parasite-infected blood in experiments, the ability of the parasites to infect the mosquito was sharply reduced as well. These results suggest that the biopesticide overall could have a very potent effect at reducing malaria transmission.
The researchers' results so far suggest that the biopesticide works by modifying the activity of a key detoxification enzyme in mosquitoes, essentially turning the insects' detox systems against them—which would explain why the biopesticide has such a strong synergy with chemical pesticides.
The researchers now plan to seek U.S. Environmental Protection Agency approval for the new biopesticide, and to set up larger-scale field tests to further assess its ability to reduce malaria incidence.
They also plan more experiments to identify the component or components of the Chromobacterium that account for its potent anti-mosquito effects.
"It was never my intention to focus on biopesticides," says Dimopoulos, whose primary focus has been malaria mosquito immunity. "But that's how these discoveries have worked out, and it's exciting that we've identified something novel with malaria control potential."
"Chromobacterium biopesticide overcomes insecticide resistance in malaria vector mosquitoes" was co-authored by Chinmay Tikhe, Sare Issiaka, Yuemei Dong, Mary Kefi, Mihra Tavadia, Etienne Bilgo, Rodrigo Corder, John Marshall, Abdoulaye Diabate, and George Dimopoulos.
Funding was provided by the U.S. Agency for International Development (USAID), the Innovative Vector Control Consortium, and the Johns Hopkins Malaria Research Institute.
