期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2015
卷号：112
期号：49
页码：15178-15183
DOI：10.1073/pnas.1520426112
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificancePlasmodium falciparum malaria originated in Africa but became global as humans migrated around the world. It is now transmitted by many different anopheline mosquito species, but little is known about the adaptation of Plasmodium to different vectors. Here, we show that the mosquito immune system is a major barrier for some P. falciparum isolates to infect mosquitoes from a different continent. Pfs47 is a protein that makes parasites "invisible" to the mosquito immune system. We found that parasites expressing a Pfs47 haplotype compatible with a given vector species can evade mosquito immunity. These findings suggest that Pfs47-mediated evasion of the mosquito immunity was critical for malaria globalization and may be a key target to disrupt disease transmission. Plasmodium falciparum malaria originated in Africa and became global as humans migrated to other continents. During this journey, parasites encountered new mosquito species, some of them evolutionarily distant from African vectors. We have previously shown that the Pfs47 protein allows the parasite to evade the mosquito immune system of Anopheles gambiae mosquitoes. Here, we investigated the role of Pfs47-mediated immune evasion in the adaptation of P. falciparum to evolutionarily distant mosquito species. We found that P. falciparum isolates from Africa, Asia, or the Americas have low compatibility to malaria vectors from a different continent, an effect that is mediated by the mosquito immune system. We identified 42 different haplotypes of Pfs47 that have a strong geographic population structure and much lower haplotype diversity outside Africa. Replacement of the Pfs47 haplotypes in a P. falciparum isolate is sufficient to make it compatible to a different mosquito species. Those parasites that express a Pfs47 haplotype compatible with a given vector evade antiplasmodial immunity and survive. We propose that Pfs47-mediated immune evasion has been critical for the globalization of P. falciparum malaria as parasites adapted to new vector species. Our findings predict that this ongoing selective force by the mosquito immune system could influence the dispersal of Plasmodium genetic traits and point to Pfs47 as a potential target to block malaria transmission. A new model, the "lock-and-key theory" of P. falciparum globalization, is proposed, and its implications are discussed.
