The deadliest form of malaria is caused by the microbe Plasmodium falciparum, which spreads through infected mosquitoes. This malarial parasite originated in Africa, and as humans migrated to other continents, it encountered new mosquito species – some of which are evolutionarily distant from the African vectors. Exactly how Plasmodium adapted to so many different vectors has been a mystery. Now in the Proceedings of the National Academy of Sciences this week, researchers report a gene that controls Plasmodium’s ability to be transmitted by mosquitoes around the world.
Anopheline mosquitoes from the subgenus Nyssorhynchus (in Central and South America), diverged from the subgenus Cellia (in Africa, India, and South Asia) about 100 million years ago. And while Plasmodium falciparum is transmitted by more than 70 different mosquito species worldwide, not all of them are necessarily compatible with the same strains of malarial parasites. For example, Plasmodium from sub-Saharan Africa likely can’t infect mosquitoes in Asia as effectively.
A U.S. National Institutes of Health team led by Alvaro Molina-Cruz and Carolina Barillas-Mury infected female African, Southeast Asian, and South American mosquitoes – Anopheles gambiae, Anopheles dirus, and Anopheles albimanus, respectively – with Plasmodium falciparum strains from people living in Senegal, Cambodia, and Brazil. Sure enough, each mosquito species was the most susceptible to the parasite strain from the same continent as themselves. That means this parasite species has adapted to different mosquito vectors, but the mosquito immune system seems to prevent infection by foreign strains.
Mosquitos are known to mount effective anti-plasmodial responses. However, the team previously found that a protein called Pfs47 allows Plasmodium falciparum to evade detection by the mosquito immune system, and different variants of the Pfs47 gene are found on different continents. Pfs47 likely renders the parasite invisible to the bloodsuckers’s defenses by interacting with a specific mosquito receptor. Though the parasite must carry the “correct” Pfs47 variant for that mosquito species in order to survive – and be transmitted later on. When the team replaced the Pfs47 gene with a variant from another continent, the parasite became compatible to the mosquito species from that other continent, increasing susceptibility.
This Pfs47-mediated immune evasion likely enabled the globalization of the deadliest form of malaria as Plasmodium falciparum adapted to new vector species. But on the flip side, these findings also point to Pfs47 as a potential target to block malaria transmission.
Image in the text: Malaria parasites with a compatible Pfs47 haplotype evade immunity, infect the mosquito gut and are transmitted. Alvaro Molina-Cruz
