Malaria prevention programs have historically focused on protecting people from the parasite-carrying mosquitoes that spread the disease. Now, two studies out of Johns Hopkins University propose an alternative—targeting the gut bacteria of mosquitoes to stop the parasite from developing in the first place.
The Johns Hopkins teams are modifying the gut bacteria of mosquitoes, a trait that is passed on when they breed. This self-propagating control method could be used for large-scale malaria prevention programs and to supplement the current insecticide-based approach, they believe.
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One team, led by Marcelo Jacobs-Lorena, genetically modified a bacterium that spreads easily among mosquitoes and stays in their bodies over the long term. The Serratia AS1 bacteria are found in mosquitoes’ ovaries as well as their gut, where the malaria parasite develops. Female mosquitoes transmit it to their mates and to their offspring.
The researchers modified the Serratia AS1 bacteria, adding five genes that code for antimalarial proteins. They found that the modified bacteria hindered parasite development, reducing the number of early-stage parasites in treated mosquitoes by 90% compared to untreated mosquitoes.
Jacobs-Lorena and his team will scale up their experiments at the Malaria Research Institute in Zambia and hope to release their modified mosquitoes in an isolated environment to observe how the bacteria spreads in wild populations.
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The second team, led by George Dimopoulos, genetically modified the mosquitoes themselves to boost their immune response and make them resistant to malaria infection. This made the mosquitoes less likely to spread malaria to humans, but it also altered the composition of their gut bacteria and changed their mating preferences, with modified males finding unmodified, wild-type females more attractive, while modified females were more likely to mate with unmodified males.
Despite progress in controlling the spread of malaria, new mosquito-control methods are still in high demand. The World Health Organization (WHO) recommends the spraying of insecticides and the use of insecticide-treated bed nets to control the spread of the disease. While this strategy has reduced the rate of malaria diagnoses and deaths in at-risk populations in recent years, it has also caused mosquitoes in some areas to become resistant to insecticides.
Several players are working on new approaches, such vaccines, but these efforts have hit some roadblocks. A phase 3 trial showed that GlaxoSmithKline’s Mosquirix vaccine wanes in efficacy over time. And the malaria parasite’s ability to “shuffle” its genes makes it a difficult target for the immune system.
Researchers at Hopkins hope that fundamentally changing the guts of the insects will prove to be a useful solution. In Dimopoulos’ lab, for example, genetically modified mosquitoes made up about 90% of the population after one generation; their numbers have stayed at this level for 10 generations. This colony of modified mosquitoes has lived in the lab for seven years, and the team now plans to study them in larger environments.
"We believe that by changing the microbiota we're changing the scent of modified mosquitoes—which in turn alters mating preference," Dimopoulos said. "It's the perfect change in mating preference in this case, because it maximizes the chances of producing genetically modified offspring when mosquitoes compete for mates."