NIH Research Festival
FARE Award Winner
Malaria is a life-threatening disease caused by Plasmodium falciparum parasites that are transmitted to people through the bites of infected anopheline mosquitoes. P. falciparum dispersed from Africa as a result of human migration which required them to adapt to several different indigenous mosquitoes. The mosquito immune system can greatly limit infection and P. falciparum evolved a strategy to evade these responses mediated by Pfs47. Pfs47 is a polymorphic gene with signatures of diversifying selection and a strong geographic genetic structure. The high genetic diversity of Pfs47 detected in Africa is reduced in Asia and has only one representative haplotype in the Americas. We hypothesize that the reduced genetic diversity of Pfs47 in Asia and the Americas, is due, at least in part, to natural selection of the parasite by the immune system of evolutionarily distant anophelines. To test this, four lines with the same genetic background were generated, in which the Pfs47 gene was deleted and complemented with the most representative haplotypes of Pfs47 from each continent. The Pfs47 KO line generated has a low infectivity in vectors from Africa, Asia and the Americas but infection was rescued by disrupting the mosquito complement-like system. Complementation of the Pfs47 KO line with distinct geographically representative haplotypes of Pfs47 recovered infection depending on the geographic origin of the vector. These results show that replacement of Pfs47 haplotypes is sufficient to change the compatibility of P. falciparum to evolutionarily diverse anopheline vectors, by allowing the parasite to evade the mosquito complement-like system.
Scientific Focus Area: Microbiology and Infectious Diseases
This page was last updated on Friday, March 26, 2021