Authors

Discussion

Plasmodium knowlesi, a simian zoonosis, is a significant cause of morbidity and mortality in South East Asia and is now the dominant cause of malaria in Malaysia. The capacity of P. knowlesi to infect humans and macaques means it is the only human Plasmodium species with a significant animal reservoir, which creates significant challenges for control. We previously adapted P. knowlesi to in vitro culture in human red blood cells (RBC) and demonstrated that these parasites are highly amenable to genetic manipulation. Here we demonstrate that P. knowlesi Normocyte Binding Protein Xa (NBPXa), a specific erythrocyte binding protein in the reticulocyte binding like/reticulocyte binding homologue (RBL/RH) family, is essential for the invasion of human red blood cells (RBC). The gene was implicated in comparisons of de novo genome assemblies of parasite lines generated during in vitro adaptation, and disruption of the gene encoding NBPXa showed that it is required for invasion of human but not macaque RBC. NBPXa is a target for vaccine design and genetic variation within NBPXa may have important implications for disease severity and the potential for human to human transmission.