Biomedicine

Fighting Malaria Inside a Mosquito's Guts

Bacteria have been genetically modified to kill the parasite that causes malaria, before people can be infected.

A study suggests that genetically modified bacteria could fight malaria from inside mosquitoes.

Global health organizations have long tried to combat malaria using bed nets and insecticides to target disease-carrying mosquitoes. But malaria continues to exact a huge toll, killing over a million people each year (see “Winning the War Against Malaria”).

Another strategy is to genetically engineer mosquitoes that are resistant to the malaria parasite. Roughly a decade ago, Johns Hopkins researcher Marcelo Jacobs-Lorena produced such mosquitoes, which generated their own antimalarial peptides, in work that appeared in Nature (see “Malaria-Resistant Mosquitoes”). This approach seemed promising in the lab, but has been difficult to implement in the field.

One reason is that even if researchers released millions of genetically modified mosquitoes in a particular area, those insects wouldn’t necessarily spread or outcompete the other mosquitoes already present unless they had some other genetic advantage, says Jacobs-Lorena.

He and his team have now taken a different approach: instead of manipulating mosquitoes directly, they have focused on the bacteria that live symbiotically in the mosquitoes’ gut, and engineered them to produce compounds that interfere with the parasite’s development.

The malaria parasite, called Plasmodium falciparum, must complete a crucial part of its life cycle within a mosquito’s midgut before it can be transmitted to people. So bacteria in that compartment are well positioned to deliver antimalarial compounds. When the mosquito takes a blood meal—that is, when it bites someone—bacteria in the mosquito’s midgut also proliferate, thanks to the blood nutrients.

Glowing gut: This image shows transgenic bacteria in a mosquito midgut. The bacteria shown here was tagged with a fluorescent protein to make it visible.

“It’s very practical and very clever,” says Jesus Valenzuela, a malaria expert at the National Institute of Allergy and Infectious Diseases.

In work that appears online today in the Proceedings of the National Academy of Sciences, Jacobs-Lorena soaked cotton balls in a suspension of sugar and genetically modified bacteria and allowed mosquitoes to feed on them. The bacteria took up residence in the mosquitoes’ midgut and appeared to stay there. Then he and his team fed the mosquitoes a blood meal infected with Plasmodium.

Jacobs-Lorena and his team had engineered the bacteria to secrete several different antimalarial peptides. The most effective two were scorpine, a peptide that inserts itself into the parasite’s membrane, causing it to leak; and EPIP, which prevents the parasite from invading the mosquito’s midgut.

Of the mosquitoes that harbored scorpine-producing or EPIP-producing bacteria, only 14 percent or 18 percent, respectively, became infected with the parasite. Of the control mosquitoes, by contrast, fully 90 percent became infected.

Jacobs-Lorena says the next step is to test this approach in a real-world environment. Researchers are still trying to figure out how they might introduce genetically engineered bacteria in the field. One option might be to leave clay pots containing sugar- and bacteria-laden cotton balls in various locations around a village where mosquitoes are likely to feed, he says.

Jacobs-Lorena and his team would also need to convince local populations and regulatory agencies to permit them to try this approach. The engineered bacteria do not appear to pose a threat to other animals or people. But, he adds, “whenever you talk about genetically modified organisms in nature, it can be touchy.” 

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