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Adaptation of Plasmodium falciparum to humans involved the loss of an ape-specific erythrocyte invasion ligand

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Liu, Weimin 
Kemp, Alison 


Abstract: Plasmodium species are frequently host-specific, but little is currently known about the molecular factors restricting host switching. This is particularly relevant for P. falciparum, the only known human-infective species of the Laverania sub-genus, all other members of which infect African apes. Here we show that all tested P. falciparum isolates contain an inactivating mutation in an erythrocyte invasion associated gene, PfEBA165, the homologues of which are intact in all ape-infective Laverania species. Recombinant EBA165 proteins only bind ape, not human, erythrocytes, and this specificity is due to differences in erythrocyte surface sialic acids. Correction of PfEBA165 inactivating mutations by genome editing yields viable parasites, but is associated with down regulation of both PfEBA165 and an adjacent invasion ligand, which suggests that PfEBA165 expression is incompatible with parasite growth in human erythrocytes. Pseudogenization of PfEBA165 may represent a key step in the emergence and evolution of P. falciparum.



Article, /631/326/417/1716, /631/326/417/2548, /692/699/255/1629, /13, /13/106, /13/31, /38/91, /82/80, article

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Nature Communications

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Nature Publishing Group UK
U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) (AI091595, R01 AI091595, R37 AI050529, R01 AI120810, T32 007532, P30 AI045008)
Wellcome Trust (Wellcome) (206194/Z/17/Z, 206194/Z/17/Z)
U.S. Department of Health & Human Services | National Institutes of Health (NIH) (R01 AI091595)