Structural changes of Plasmodium falciparum during early development in the human erythrocyte revealed by correlative live-cell imaging and serial section electron microscopy

Electron microscopy (EM) is an essential tool to understand the Plasmodium spp. lifecycle at the ultrastructural level, but it is difficult to interpret parasite behavior with EM images alone. The remodeling of parasite shape after P. falciparum invasion of host red blood cell is a dynamic and fast-progressing event that complicates ultrastructural analysis. Additionally, the asynchrony and low frequency of merozoite invasion in vitro hampers the study of this phenomenon by traditional EM. To overcome these challenges, we developed a correlative light-electron microscopy (CLEM) approach that permits individual parasites to be recorded by time-lapse microscopy during parasite egress, invasion, and shape remodeling, and then visualized by transmission EM.