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.
KAUST Repository Item: Exported on 2020-10-01
Acknowledgements: This work was supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK, the UK Medical Research Council (MRC), and the Wellcome Trust. The work was further supported by the UK MRC (Grants U117532063 and U117532067), the European Community's Seventh Framework Programme under Grant Agreement 242095 (EviMalar), an MRC Career Development Award (to R.W.M.) jointly funded by the UK MRC and Department for International Development, and the faculty baseline fund (BRF) from the King Abdullah University of Science and Technology (to A.P.). A.A. and Y.L.L. were funded by a UM High Impact Research (HIR) Grant UM-MOHE (UM.C/HIR/MOHE/MED/16) from the Ministry of Higher Education Malaysia.