Authors
R Moon1; 1 London School of Hygiene and Tropical Medicine, UK Discussion
The adaptation of P. knowlesi (Pk) to culture in human erythrocytes has provided exciting opportunities to investigate erythrocyte invasion biology. Two major protein families, the erythrocyte binding-like proteins (EBPs/EBAs) and the reticulocyte binding-like proteins (RBLs/RHs) have been studied extensively in P. falciparum (Pf) and are hypothesized to have overlapping, but critical roles during the invasion process. Pk has a smaller repertoire, including one EBL(DBPa) and one RBL(NBPXa) that are both essential for invasion of human erythrocytes. By taking advantage of the unique biological features of Pk, which have merozoites double the size of Pf, we have used live microscopic analysis to develop a deeper understanding of the distinct stages of invasion, as well as the roles of the Pk EBP/RBL families within this process. Using a conditional DiCre approach we have demonstrated distinct roles for the two families at different stages in invasion. We also uncovered new features that caused us to reassess invasion including that Pk merozoites are able to undergo productive gliding motility prior to invasion and merozoite topology was the opposite to how we expected! These findings have revealed new features of this complex process, as well as new tools and techniques to deepen our understanding of this process in all malaria parasite species. 
