But no matter how effective the engineered microbes are in the lab, they’re useless unless you can find a way of spreading them through wild mosquitoes. That problem stumped Jacobs-Lorena for years, until one of his team members, Sibao Wang, made a fortuitous discovery.
Wang was dissecting the ovaries of a captive malarial mosquito when he noticed that the fluid leaking out of the organs was a little cloudy. And when he dabbed the fluid onto petri dishes full of nutritious jelly, bacteria started to grow. These bacteria were all the same, and though they belonged to a group called Serratia, they were also part of a strain that no one had seen before. The team called it AS1.
AS1 was everything the team could have wished for. It can be engineered to carry the same anti-Plasmodium genes that the team added into Pantoea. But unlike that other bacterium, AS1 spreads like wildfire. It can travel throughout the body of an infected insect. When it infects the reproductive glands of male mosquitoes, it can spread to females through sex. When it infect the ovaries of a female, it can stick to her eggs. And when those eggs are laid in water, the bacteria swim around and get ingested by the mosquito larvae that eventually hatch.
So AS1 can spread effectively within generations, and into new ones. Wang demonstrated this by releasing infected mosquitoes into cages with uninfected peers, who outnumbered them by 20 to one. Within a single generation, every mosquito in the cage carried Serratia.
The team is now planning to take their mosquitoes to a field station in Zambia, and release them into a net-covered greenhouse that contains vegetation and a little hut. They want to know if AS1 will still spread effectively in these more realistic settings.
But Alison Isaacs, from the London School of Hygiene and Tropical Medicine, notes that AS1 is very similar to Serratia strains that are common in other insects. “It will be important to investigate whether the genetically modified bacteria could spread beyond mosquitoes, and identify the associated risks,” she says. One way to prevent such cross-species jumps would be to insert the antimalarial genes not into a symbiotic microbe, but directly into the genomes of the mosquitoes themselves. Jacobs-Lorena’s group have been trying to do that, too, and so has another team led by George Dimopoulos, from Johns Hopkins University.
In 2006, Dimopoulos’s team showed that when mosquitoes are invaded with Plasmodium parasites, they mount an immune response to clear the infections. But they’re usually too late; by the time they react, the parasites have already colonized their guts. So the team gave the insects an edge by tweaking a gene called REL2, which then revved up their immune systems as soon as they started sucking blood. And these modified mosquitoes were indeed more resistant to malaria.