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Pathogenicity Determinants of the Human Malaria Parasite Plasmodium falciparum Have Ancient Origins

Plasmodium falciparum, the most deadly of the human malaria parasites, is a member of the Laverania subgenus that also infects African Great Apes. The virulence of P. falciparum is related to cytoadhesion of infected erythrocytes in microvasculature, but the origin of dangerous parasite adhesion tra...

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Autores principales: Brazier, Andrew J., Avril, Marion, Bernabeu, Maria, Benjamin, Maxwell, Smith, Joseph D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5227068/
https://www.ncbi.nlm.nih.gov/pubmed/28101534
http://dx.doi.org/10.1128/mSphere.00348-16
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author Brazier, Andrew J.
Avril, Marion
Bernabeu, Maria
Benjamin, Maxwell
Smith, Joseph D.
author_facet Brazier, Andrew J.
Avril, Marion
Bernabeu, Maria
Benjamin, Maxwell
Smith, Joseph D.
author_sort Brazier, Andrew J.
collection PubMed
description Plasmodium falciparum, the most deadly of the human malaria parasites, is a member of the Laverania subgenus that also infects African Great Apes. The virulence of P. falciparum is related to cytoadhesion of infected erythrocytes in microvasculature, but the origin of dangerous parasite adhesion traits is poorly understood. To investigate the evolutionary history of the P. falciparum cytoadhesion pathogenicity determinant, we studied adhesion domains from the chimpanzee malaria parasite P. reichenowi. We demonstrate that the P. reichenowi var gene repertoire encodes cysteine-rich interdomain region (CIDR) domains which bind human CD36 and endothelial protein C receptor (EPCR) with the same levels of affinity and at binding sites similar to those bound by P. falciparum. Moreover, P. reichenowi domains interfere with the protective function of the activated protein C-EPCR pathway on endothelial cells, a presumptive virulence trait in humans. These findings provide evidence for ancient evolutionary origins of two key cytoadhesion properties of P. falciparum that contribute to human infection and pathogenicity. IMPORTANCE Cytoadhesion of P. falciparum-infected erythrocytes in the microcirculation is a major virulence determinant. P. falciparum is descended from a subgenus of parasites that also infect chimpanzees and gorillas and exhibits strict host species specificity. Despite their high genetic similarity to P. falciparum, it is unknown whether ape parasites encode adhesion properties similar to those of P. falciparum or are as virulent in their natural hosts. Consequently, it has been unclear when virulent adhesion traits arose in P. falciparum and how long they have been present in the parasite population. It is also unknown whether cytoadhesive interactions pose a barrier to cross-species transmission. We show that parasite domains from the chimpanzee malaria parasite P. reichenowi bind human receptors with specificity similar to that of P. falciparum. Our findings suggest that parasite adhesion traits associated with both mild and severe malaria have much earlier origins than previously appreciated and have important implications for virulence evolution in a major human pathogen.
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spelling pubmed-52270682017-01-18 Pathogenicity Determinants of the Human Malaria Parasite Plasmodium falciparum Have Ancient Origins Brazier, Andrew J. Avril, Marion Bernabeu, Maria Benjamin, Maxwell Smith, Joseph D. mSphere Research Article Plasmodium falciparum, the most deadly of the human malaria parasites, is a member of the Laverania subgenus that also infects African Great Apes. The virulence of P. falciparum is related to cytoadhesion of infected erythrocytes in microvasculature, but the origin of dangerous parasite adhesion traits is poorly understood. To investigate the evolutionary history of the P. falciparum cytoadhesion pathogenicity determinant, we studied adhesion domains from the chimpanzee malaria parasite P. reichenowi. We demonstrate that the P. reichenowi var gene repertoire encodes cysteine-rich interdomain region (CIDR) domains which bind human CD36 and endothelial protein C receptor (EPCR) with the same levels of affinity and at binding sites similar to those bound by P. falciparum. Moreover, P. reichenowi domains interfere with the protective function of the activated protein C-EPCR pathway on endothelial cells, a presumptive virulence trait in humans. These findings provide evidence for ancient evolutionary origins of two key cytoadhesion properties of P. falciparum that contribute to human infection and pathogenicity. IMPORTANCE Cytoadhesion of P. falciparum-infected erythrocytes in the microcirculation is a major virulence determinant. P. falciparum is descended from a subgenus of parasites that also infect chimpanzees and gorillas and exhibits strict host species specificity. Despite their high genetic similarity to P. falciparum, it is unknown whether ape parasites encode adhesion properties similar to those of P. falciparum or are as virulent in their natural hosts. Consequently, it has been unclear when virulent adhesion traits arose in P. falciparum and how long they have been present in the parasite population. It is also unknown whether cytoadhesive interactions pose a barrier to cross-species transmission. We show that parasite domains from the chimpanzee malaria parasite P. reichenowi bind human receptors with specificity similar to that of P. falciparum. Our findings suggest that parasite adhesion traits associated with both mild and severe malaria have much earlier origins than previously appreciated and have important implications for virulence evolution in a major human pathogen. American Society for Microbiology 2017-01-11 /pmc/articles/PMC5227068/ /pubmed/28101534 http://dx.doi.org/10.1128/mSphere.00348-16 Text en Copyright © 2017 Brazier et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (http://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Brazier, Andrew J.
Avril, Marion
Bernabeu, Maria
Benjamin, Maxwell
Smith, Joseph D.
Pathogenicity Determinants of the Human Malaria Parasite Plasmodium falciparum Have Ancient Origins
title Pathogenicity Determinants of the Human Malaria Parasite Plasmodium falciparum Have Ancient Origins
title_full Pathogenicity Determinants of the Human Malaria Parasite Plasmodium falciparum Have Ancient Origins
title_fullStr Pathogenicity Determinants of the Human Malaria Parasite Plasmodium falciparum Have Ancient Origins
title_full_unstemmed Pathogenicity Determinants of the Human Malaria Parasite Plasmodium falciparum Have Ancient Origins
title_short Pathogenicity Determinants of the Human Malaria Parasite Plasmodium falciparum Have Ancient Origins
title_sort pathogenicity determinants of the human malaria parasite plasmodium falciparum have ancient origins
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5227068/
https://www.ncbi.nlm.nih.gov/pubmed/28101534
http://dx.doi.org/10.1128/mSphere.00348-16
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