July 7, 2019  |  

Normocyte-binding protein required for human erythrocyte invasion by the zoonotic malaria parasite Plasmodium knowlesi.

Authors: Moon, Robert W and Sharaf, Hazem and Hastings, Claire H and Ho, Yung Shwen and Nair, Mridul B and Rchiad, Zineb and Knuepfer, Ellen and Ramaprasad, Abhinay and Mohring, Franziska and Amir, Amirah and Yusuf, Noor A and Hall, Joanna and Almond, Neil and Lau, Yee Ling and Pain, Arnab and Blackman, Michael J and Holder, Anthony A

The dominant cause of malaria in Malaysia is now Plasmodium knowlesi, a zoonotic parasite of cynomolgus macaque monkeys found throughout South East Asia. Comparative genomic analysis of parasites adapted to in vitro growth in either cynomolgus or human RBCs identified a genomic deletion that includes the gene encoding normocyte-binding protein Xa (NBPXa) in parasites growing in cynomolgus RBCs but not in human RBCs. Experimental deletion of the NBPXa gene in parasites adapted to growth in human RBCs (which retain the ability to grow in cynomolgus RBCs) restricted them to cynomolgus RBCs, demonstrating that this gene is selectively required for parasite multiplication and growth in human RBCs. NBPXa-null parasites could bind to human RBCs, but invasion of these cells was severely impaired. Therefore, NBPXa is identified as a key mediator of P. knowlesi human infection and may be a target for vaccine development against this emerging pathogen.

Journal: Proceedings of the National Academy of Sciences of the United States of America
DOI: 10.1073/pnas.1522469113
Year: 2016

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