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Ancient human sialic acid variant restricts an emerging zoonotic malaria parasite

Author

Listed:
  • Selasi Dankwa

    (Harvard T.H. Chan School of Public Health)

  • Caeul Lim

    (Harvard T.H. Chan School of Public Health)

  • Amy K. Bei

    (Harvard T.H. Chan School of Public Health)

  • Rays H. Y. Jiang

    (Harvard T.H. Chan School of Public Health)

  • James R. Abshire

    (Massachusetts Institute of Technology)

  • Saurabh D. Patel

    (Harvard T.H. Chan School of Public Health
    Hepatology and Nutrition, Boston Children’s Hospital)

  • Jonathan M. Goldberg

    (Harvard T.H. Chan School of Public Health)

  • Yovany Moreno

    (Harvard T.H. Chan School of Public Health)

  • Maya Kono

    (Harvard T.H. Chan School of Public Health)

  • Jacquin C. Niles

    (Massachusetts Institute of Technology)

  • Manoj T. Duraisingh

    (Harvard T.H. Chan School of Public Health)

Abstract

Plasmodium knowlesi is a zoonotic parasite transmitted from macaques causing malaria in humans in Southeast Asia. Plasmodium parasites bind to red blood cell (RBC) surface receptors, many of which are sialylated. While macaques synthesize the sialic acid variant N-glycolylneuraminic acid (Neu5Gc), humans cannot because of a mutation in the enzyme CMAH that converts N-acetylneuraminic acid (Neu5Ac) to Neu5Gc. Here we reconstitute CMAH in human RBCs for the reintroduction of Neu5Gc, which results in enhancement of P. knowlesi invasion. We show that two P. knowlesi invasion ligands, PkDBPβ and PkDBPγ, bind specifically to Neu5Gc-containing receptors. A human-adapted P. knowlesi line invades human RBCs independently of Neu5Gc, with duplication of the sialic acid-independent invasion ligand, PkDBPα and loss of PkDBPγ. Our results suggest that absence of Neu5Gc on human RBCs limits P. knowlesi invasion, but that parasites may evolve to invade human RBCs through the use of sialic acid-independent pathways.

Suggested Citation

  • Selasi Dankwa & Caeul Lim & Amy K. Bei & Rays H. Y. Jiang & James R. Abshire & Saurabh D. Patel & Jonathan M. Goldberg & Yovany Moreno & Maya Kono & Jacquin C. Niles & Manoj T. Duraisingh, 2016. "Ancient human sialic acid variant restricts an emerging zoonotic malaria parasite," Nature Communications, Nature, vol. 7(1), pages 1-9, September.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11187
    DOI: 10.1038/ncomms11187
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