Invasion of red blood cells (RBCs) by Plasmodium merozoites is critical to their continued survival within the host. Two major protein families, the Duffy binding-like proteins (DBPs/EBAs) and the reticulocyte binding like proteins (RBLs/RHs) have been studied extensively in P. falciparum and are hypothesized to have overlapping, but critical roles just prior to host cell entry. The zoonotic malaria parasite, P. knowlesi , has larger invasive merozoites and contains a smaller, less redundant, DBP and RBL repertoire than P. falciparum . One DBP (DBPα) and one RBL, normocyte binding protein Xa (NBPXa) are essential for invasion of human RBCs. Taking advantage of the unique biological features of P. knowlesi and iterative CRISPR-Cas9 genome editing, we determine the precise order of key invasion milestones and demonstrate distinct roles for each family. These distinct roles support a mechanism for phased commitment to invasion and can be targeted synergistically with invasion inhibitory antibodies. Malaria parasites invade erythrocytes to proliferate, but visualizing this rapid process is challenging. Here the authors use live imaging and genome-editing of P. knowlesi to dissect invasion and establish the roles of two vital parasite proteins.
【저자키워드】 Pathogens, CRISPR-Cas9 genome editing, Parasitology, Parasite biology, Cellular microbiology,