A malarial mosquito is a flying factory for Plasmodium – a parasite that fills its guts, and storms the blood of every person it bites. By hosting and spreading these parasites, mosquitoes kill 1.2 million people every year.
But Plasmodium isn’t the only thing living inside a mosquito’s guts. Just as our bowels are home to trillions of bacteria, mosquitoes also carry their own microscopic menageries.
Now, Sibao Wang from Johns Hopkins Bloomberg School of Public Health has transformed one of these bacterial associates into the latest recruit in our war against malaria.
By loading it with genes that destroy malarial parasites, Wang has turned the friend of our enemy into our friend.
Many groups of scientists have tried to beat malaria by genetically modifying the species of mosquito that carries it – Anopheles gambiae.
Marcelo Jacobs-Lorena, who led Wang’s new study, has been at the forefront of these efforts. In 2002, his team loaded mosquitoes with a modified gene so that their guts produce a substance that kills off Plasmodium.
“The approach worked very well in the laboratory,” says Jacobs-Lorena, but it would be impossible to load wild mosquitoes with the anti-malarial gene.
Instead, you’d have to ensure that the modified mosquitoes could out-compete their wild peers, so that the gene passes from one generation to the next via natural breeding.
It must also do so quickly before the parasite can evolve a countermeasure.
That’s very difficult to guarantee, especially given our limited understanding of the mating habits and ecology of mosquitoes.
Jacobs-Lorena found an alternative. He would sneak the Plasmodium-killing gene into the bacteria that live inside a mosquito’s guts, rather than the insect’s own genome.
“We thought that it would be easier to introduce bacteria than genes into mosquitoes in the field,” he says.
The strategy has one big advantage: the gut is the most vulnerable part of Plasmodium’s complicated shape-shifting life cycle.
When the mosquito bites an infected human, it sucks up thousands of Plasmodium sex cells, which mate with each other to form fertilised eggs called ookinetes.
These invade the lining of the insect’s gut and become factories called oocysts. Each one manufactures thousands of long, worm-like sporozoites that swim into the mosquito’s salivary glands, ready to jump into a new person.
The oocyst stage is the bottleneck in this process. Even if a mosquito swallows thousands of Plasmodium cells, it typically ends up with far fewer oocysts in its gut.
In such small numbers, they make an attractive target, and it just so happens that the gut contains potential collaborators – bacteria.
Pantoea agglomerans is among the most common of these partners. It’s co-exists harmlessly with the mosquito and we still don’t know what, if any, role it performs.
Wang, a member of Jacobs-Lorena’s team, engineered P.agglomerans to make several proteins that turn the mosquito’s gut into a hostile zone for Plasmodium.
Some of these proteins interact the mosquito’s gut to prevent the young Plasmodium parasites from invading it, while others (including one derived from scorpion venom) tear the parasite apart.
The bacteria secrete these weapons into the gut where they get to work upon any invading Plasmodium.
It also helps that when a mosquito drinks blood, the numbers of P.agglomerans within it shoot up by over 100 times, creating a defence force that’s ready for the incoming parasites.
Wang found that the engineered bacteria slashed the numbers of oocysts in mosquitoes by 85 to 98 per cent.
Just 14 to 18 per cent of the insects carrying the defensive microbes became infected with Plasmodium after drinking contaminated blood, down from a typical proportion of 90 per cent.
Scientists who are trying to use GM-mosquitoes to fight dengue fever in Brazil and the US have already encountered severe hostility. The bacterial approach might fare even worse.
“It relies on a GM bacterium which can’t be contained once released in mosquito populations, and will easily end up in the food chain and eventually also on peoples plates,” says Dimopoulos.
“While such bacteria may not pose a hazard to humans and animals, the work required to prove, educate and finally convince various stakeholders that the implementation is safe will be lengthy and challenging.”
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