Normocyte-binding protein required for human erythrocyte invasion by the zoonotic malaria parasitePlasmodium knowlesi

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

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

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.
Original languageEnglish (US)
Pages (from-to)7231-7236
Number of pages6
JournalProceedings of the National Academy of Sciences
Volume113
Issue number26
DOIs
StatePublished - Jun 14 2016

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