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

William R Proto; Sasha V Siegel; Selasi Dankwa; Weimin Liu; Alison Kemp; Sarah Marsden; Zenon A Zenonos; Steve Unwin; Paul M Sharp; Gavin J Wright; Beatrice H Hahn; Manoj T Duraisingh; Julian C Rayner

doi:10.1038/s41467-019-12294-3

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

William R Proto, Sasha V Siegel, Selasi Dankwa, Weimin Liu, Alison Kemp, Sarah Marsden, Zenon A Zenonos, Steve Unwin, Paul M Sharp, Gavin J Wright, Beatrice H Hahn, Manoj T Duraisingh, Julian C Rayner

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	4512
Number of pages	12
Journal	Nature Communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-12294-3
Publication status	Published - 4 Oct 2019

Bibliographical note

Keywords

first & last 3 (QQ only)
first & last (all papers)
parasites and microbes
staffpaper

Access to Document

10.1038/s41467-019-12294-3

s41467-019-12294-3
© The Author(s) 2019
Final published version, 2.38 MBLicence: CC BY

Cite this

Proto, W. R., Siegel, S. V., Dankwa, S., Liu, W., Kemp, A., Marsden, S., Zenonos, Z. A., Unwin, S., Sharp, P. M., Wright, G. J., Hahn, B. H., Duraisingh, M. T., & Rayner, J. C. (2019). Adaptation of Plasmodium falciparum to humans involved the loss of an ape-specific erythrocyte invasion ligand. Nature Communications, 10(1), Article 4512. https://doi.org/10.1038/s41467-019-12294-3

@article{0c32a4e064e54b80a01d2455e731007f,

title = "Adaptation of Plasmodium falciparum to humans involved the loss of an ape-specific erythrocyte invasion ligand.",

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.",

keywords = "first & last 3 (QQ only), first & last (all papers), parasites and microbes, staffpaper",

author = "Proto, {William R} and Siegel, {Sasha V} and Selasi Dankwa and Weimin Liu and Alison Kemp and Sarah Marsden and Zenonos, {Zenon A} and Steve Unwin and Sharp, {Paul M} and Wright, {Gavin J} and Hahn, {Beatrice H} and Duraisingh, {Manoj T} and Rayner, {Julian C}",

note = "{\textcopyright} The Author(s) 2019 ",

year = "2019",

month = oct,

day = "4",

doi = "10.1038/s41467-019-12294-3",

language = "English",

volume = "10",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

}

TY - JOUR

T1 - Adaptation of Plasmodium falciparum to humans involved the loss of an ape-specific erythrocyte invasion ligand.

AU - Proto, William R

AU - Siegel, Sasha V

AU - Dankwa, Selasi

AU - Liu, Weimin

AU - Kemp, Alison

AU - Marsden, Sarah

AU - Zenonos, Zenon A

AU - Unwin, Steve

AU - Sharp, Paul M

AU - Wright, Gavin J

AU - Hahn, Beatrice H

AU - Duraisingh, Manoj T

AU - Rayner, Julian C

PY - 2019/10/4

Y1 - 2019/10/4

N2 - 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.

AB - 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.

KW - first & last 3 (QQ only)

KW - first & last (all papers)

KW - parasites and microbes

KW - staffpaper

U2 - 10.1038/s41467-019-12294-3

DO - 10.1038/s41467-019-12294-3

M3 - Article

SN - 2041-1723

VL - 10

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 4512

ER -