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Engineering malaria resistance in mosquitoes

Scanning electron micrograph of Plasmodium invading a mosquito midgut. NIAID

Malaria affects more than 200 million people worldwide and kills hundreds of thousands, mostly young African children. In the United States, fewer than 2,000 cases of malaria are diagnosed each year, but the disease is a serious concern for international travelers, including aid workers and military personnel. 

Malaria is caused by a single-celled parasite called Plasmodium. The parasite infects female mosquitoes when they feed on the blood of an infected person. Once in the mosquito’s midgut, the parasites multiply and migrate to the salivary glands. When the mosquito bites the next person, the parasites enter the person’s bloodstream.

Scientists have been exploring the use of genetically modified mosquitoes to prevent the spread of malaria and other diseases. One challenge is ensuring that the modified mosquitoes mate with wild mosquitoes and transfer the protective trait to their offspring.

In previous work, a team led by Dr. George Dimopoulos at Johns Hopkins University genetically modified Anopheles mosquitoes to boost immune activity in their midguts. This immune boost successfully suppressed malaria-causing Plasmodium parasites as well as bacteria. In their current study, the team examined the effects of these modifications in several generations of mosquitoes. The work was funded by NIH’s National Institute of Allergy and Infectious Diseases (NIAID). Results were published in Science on September 29, 2017.

The researchers caged equal numbers of wild and genetically modified mosquitoes and then monitored their breeding. They expected about 75% of the resulting mosquitoes to have the resistance trait. However, the trait was found in about 90% of the first mosquito generation and remained at that level through 10 generations. Even when the team mixed 10% modified mosquitoes with 90% wild ones, the resistance trait dominated after a few generations. Importantly, the modified mosquitoes maintained their resistance to the malaria parasite for 7 years.

The scientists showed that the immune boost caused changes in the microbial community, or microbiota, of both the mosquito midgut and reproductive organs. This, in turn, altered mating preferences among the mosquitoes. Genetically modified males preferred wild females, and wild males preferred modified females. These preferences helped to quickly spread the protective trait through the mosquito population.

“We believe that by changing the microbiota we’re changing the scent of modified mosquitoes—which in turn alters mating preference,” Dimopoulos says.

The results suggest that genetically modified mosquitoes can spread resistance to the malaria-causing parasite by thriving and mating with wild mosquitoes. However, this work was conducted in the laboratory. More research is needed to see whether the approach will work under natural conditions.