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

Proc Natl Acad Sci U S A. 2016 Jun 28;113(26):7231-6. doi: 10.1073/pnas.1522469113. Epub 2016 Jun 14.

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.

Keywords: Plasmodium knowlesi; invasion; malaria parasite; normocyte-binding protein; zoonotic malaria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / genetics*
  • Cells, Cultured
  • Erythrocytes / parasitology*
  • Humans
  • Macaca fascicularis
  • Macaca mulatta
  • Malaria
  • Plasmodium knowlesi / genetics*
  • Plasmodium knowlesi / pathogenicity*
  • Polymorphism, Single Nucleotide
  • Protozoan Proteins / genetics*
  • Zoonoses

Substances

  • Carrier Proteins
  • Protozoan Proteins