Development and host cell modifications of Plasmodium falciparum blood stages in four dimensions

Blood stages of Plasmodium falciparum cause the pathology of malaria; however, the progression of the parasite through this complex part of the life cycle has never been visualized. In this study, we use four-dimensional imaging to show for the first time the development of individual parasites in erythrocytes and the concomitant host cell modifications. Our data visualize an unexpectedly dynamic parasite, provide a reference for this life cycle stage and challenge the model that protein export in P. falciparum is linked to the biogenesis of host cell modifications termed Maurer's clefts. Our results provide a novel view of the blood-stage development, Maurer's cleft development and protein export in malaria parasites, and open the door to study dynamic processes, drug effects and the phenotype of mutants. The Plasmodium falciparum parasite that causes malaria has a complex life cycle in human erythrocytes. Using time-lapse three-dimensional imaging, the authors show the intraerythrocytic stages of the parasite and provide new insight into the export of P. falciparum proteins to Maurer's clefts.