Ancient human sialic acid variant restricts an emerging zoonotic malaria parasite
| Autor: | Yovany Moreno, James Robbins Abshire, Jacquin C. Niles, Selasi Dankwa, Saurabh D. Patel, Rays H. Y. Jiang, Jonathan M. Goldberg, Caeul Lim, Amy K. Bei, Manoj T. Duraisingh, Maya Kono |
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| Přispěvatelé: | Massachusetts Institute of Technology. Department of Biological Engineering, Abshire, James Robbins, Niles, Jacquin C. |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Erythrocytes Science Protozoan Proteins General Physics and Astronomy Macaque Plasmodium General Biochemistry Genetics and Molecular Biology Article Mixed Function Oxygenases 03 medical and health sciences chemistry.chemical_compound biology.animal Zoonoses Neuraminic acid parasitic diseases medicine Animals Humans Plasmodium knowlesi Multidisciplinary biology fungi food and beverages hemic and immune systems General Chemistry medicine.disease biology.organism_classification Virology N-Acetylneuraminic Acid 3. Good health Sialic acid Malaria Red blood cell 030104 developmental biology medicine.anatomical_structure HEK293 Cells chemistry Neuraminic Acids N-Acetylneuraminic acid Genome Protozoan circulatory and respiratory physiology |
| Zdroj: | Nature Communications Nature Communications, Vol 7, Iss 1, Pp 1-9 (2016) Nature Publishing Group |
| ISSN: | 2041-1723 |
| Popis: | 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. National Institutes of Health (U.S.) (grant AI091787) Centers for Disease Control and Prevention (U.S.) (grant (R36-CK000119-01)) National Institutes of Health (U.S.) (Epidemiology of Infectious Disease and Biodefense Training Grant, 2-T32-AI007535-12) |
| Databáze: | OpenAIRE |
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