Ancient human sialic acid variant restricts an emerging zoonotic malaria parasite
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), h...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
Springer Nature
2016
|
| Online Access: | http://hdl.handle.net/1721.1/103124 https://orcid.org/0000-0002-6250-8796 |
| _version_ | 1811086737765564416 |
|---|---|
| author | Dankwa, Selasi Lim, Caeul Bei, Amy K. Jiang, Rays H. Y. Abshire, James Robbins Patel, Saurabh D. Goldberg, Jonathan M. Moreno, Yovany Kono, Maya Niles, Jacquin C. Duraisingh, Manoj T. |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Dankwa, Selasi Lim, Caeul Bei, Amy K. Jiang, Rays H. Y. Abshire, James Robbins Patel, Saurabh D. Goldberg, Jonathan M. Moreno, Yovany Kono, Maya Niles, Jacquin C. Duraisingh, Manoj T. |
| author_sort | Dankwa, Selasi |
| collection | MIT |
| 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. |
| first_indexed | 2024-09-23T13:32:30Z |
| format | Article |
| id | mit-1721.1/103124 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:32:30Z |
| publishDate | 2016 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | mit-1721.1/1031242022-10-01T15:42:27Z Ancient human sialic acid variant restricts an emerging zoonotic malaria parasite Dankwa, Selasi Lim, Caeul Bei, Amy K. Jiang, Rays H. Y. Abshire, James Robbins Patel, Saurabh D. Goldberg, Jonathan M. Moreno, Yovany Kono, Maya Niles, Jacquin C. Duraisingh, Manoj T. Massachusetts Institute of Technology. Department of Biological Engineering Abshire, James Robbins Niles, Jacquin C. 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) 2016-06-16T19:27:14Z 2016-06-16T19:27:14Z 2016-04 2015-08 Article http://purl.org/eprint/type/JournalArticle 2041-1723 http://hdl.handle.net/1721.1/103124 Dankwa, Selasi, Caeul Lim, Amy K. Bei, Rays H. Y. Jiang, James R. Abshire, Saurabh D. Patel, Jonathan M. Goldberg, et al. “Ancient Human Sialic Acid Variant Restricts an Emerging Zoonotic Malaria Parasite.” Nat Comms 7 (April 4, 2016): 11187. https://orcid.org/0000-0002-6250-8796 en_US http://dx.doi.org/10.1038/ncomms11187 Nature Communications Creative Commons Attribution http://creativecommons.org/licenses/by/4.0/ application/pdf Springer Nature Nature Publishing Group |
| spellingShingle | Dankwa, Selasi Lim, Caeul Bei, Amy K. Jiang, Rays H. Y. Abshire, James Robbins Patel, Saurabh D. Goldberg, Jonathan M. Moreno, Yovany Kono, Maya Niles, Jacquin C. Duraisingh, Manoj T. Ancient human sialic acid variant restricts an emerging zoonotic malaria parasite |
| title | Ancient human sialic acid variant restricts an emerging zoonotic malaria parasite |
| title_full | Ancient human sialic acid variant restricts an emerging zoonotic malaria parasite |
| title_fullStr | Ancient human sialic acid variant restricts an emerging zoonotic malaria parasite |
| title_full_unstemmed | Ancient human sialic acid variant restricts an emerging zoonotic malaria parasite |
| title_short | Ancient human sialic acid variant restricts an emerging zoonotic malaria parasite |
| title_sort | ancient human sialic acid variant restricts an emerging zoonotic malaria parasite |
| url | http://hdl.handle.net/1721.1/103124 https://orcid.org/0000-0002-6250-8796 |
| work_keys_str_mv | AT dankwaselasi ancienthumansialicacidvariantrestrictsanemergingzoonoticmalariaparasite AT limcaeul ancienthumansialicacidvariantrestrictsanemergingzoonoticmalariaparasite AT beiamyk ancienthumansialicacidvariantrestrictsanemergingzoonoticmalariaparasite AT jiangrayshy ancienthumansialicacidvariantrestrictsanemergingzoonoticmalariaparasite AT abshirejamesrobbins ancienthumansialicacidvariantrestrictsanemergingzoonoticmalariaparasite AT patelsaurabhd ancienthumansialicacidvariantrestrictsanemergingzoonoticmalariaparasite AT goldbergjonathanm ancienthumansialicacidvariantrestrictsanemergingzoonoticmalariaparasite AT morenoyovany ancienthumansialicacidvariantrestrictsanemergingzoonoticmalariaparasite AT konomaya ancienthumansialicacidvariantrestrictsanemergingzoonoticmalariaparasite AT nilesjacquinc ancienthumansialicacidvariantrestrictsanemergingzoonoticmalariaparasite AT duraisinghmanojt ancienthumansialicacidvariantrestrictsanemergingzoonoticmalariaparasite |