title: Plasmodium evasion of mosquito immunity and global malaria transmission: The lock-and-key theory.
abstract: 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.
authors.affiliation: Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852 cbarillas@niaid.nih.gov amolina-cruz@niaid.nih.gov.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Molina-Cruz
authors.affiliation: Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852.
authors.forename: Gaspar E
authors.initials: GE
authors.lastname: Canepa
authors.affiliation: Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852.
authors.forename: Nitin
authors.initials: N
authors.lastname: Kamath
authors.affiliation: Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852.
authors.forename: Noelle V
authors.initials: NV
authors.lastname: Pavlovic
authors.affiliation: Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852.
authors.forename: Jianbing
authors.initials: J
authors.lastname: Mu
authors.affiliation: Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852.
authors.forename: Urvashi N
authors.initials: UN
authors.lastname: Ramphul
authors.affiliation: Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852.
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Ramirez
authors.affiliation: Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852 cbarillas@niaid.nih.gov amolina-cruz@niaid.nih.gov.
authors.forename: Carolina
authors.initials: C
authors.lastname: Barillas-Mury
mesh_terms: D000818:Animals; D000852:Anopheles / Q000276:immunology* / Q000469:parasitology; D057131:Immune Evasion; D007303:Insect Vectors; D016778:Malaria, Falciparum / Q000635:transmission*; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000502:physiology*
keywords: Pfs47; Plasmodium selection; anopheles immunity; immune evasion; malaria globalization