Ancient human sialic acid variant restricts an emerging zoonotic malaria parasite

Details

• Alternative Title:
  Nat Commun
• Personal Author:
  Dankwa, Selasi ; Lim, Caeul ; Bei, Amy K. ; Jiang, Rays H. Y. ; Abshire, James R. ; Patel, Saurabh D. ; Goldberg, Jonathan M. ; Moreno, Yovany ; Kono, Maya ; Niles, Jacquin C. ; Duraisingh, Manoj T.
• Description:
  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.
• Subjects:
  Animals Erythrocytes Genome, Protozoan HEK293 Cells Humans Malaria Mixed Function Oxygenases N-Acetylneuraminic Acid Neuraminic Acids Plasmodium Knowlesi Protozoan Proteins Zoonoses

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• Source:
  Nat Commun. 2016; 7.
• Pubmed ID:
  27041489
• Pubmed Central ID:
  PMC4822025
• Document Type:
  Journal Article
• Funding:
  1DP2OD007124/OD/NIH HHS/United States ; 2-T32-AI007535-12/AI/NIAID NIH HHS/United States ; 5-K12-HD000850/HD/NICHD NIH HHS/United States ; 5-T32-GM08334/GM/NIGMS NIH HHS/United States ; AI091787/AI/NIAID NIH HHS/United States ; P50-GM098792/GM/NIGMS NIH HHS/United States ; R36-CK000119-01/CK/NCEZID CDC HHS/United States ; T32 GM008334/GM/NIGMS NIH HHS/United States
• Volume:
  7
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:60107c0697c2c9e9d4ac79805a696d9636ef277c41a287972a293e30fb5fb49a
• Download URL:
  https://stacks.cdc.gov/view/cdc/41037/cdc_41037_DS1.pdf
• File Type:
  [PDF - 1.32 MB ]