The malaria parasite Plasmodium falciparum prepares for life within the host cell by activating a complex gene network

The intraerythrocytic developmental cycle (IDC) during which the malaria parasite Plasmodium falciparum multiplies asexually within the human host red blood cell is the symptomatic stage of the malaria parasite life cycle. The IDC lasts 48-hours and it initiates when parasite stages called merozoites are released into the bloodstream, following schizont rupture, and invade the host red blood cells. Within the host, the parasite transforms into the ring stage. The merozoite stage is the less studied stage of the IDC, despite its importance for the establishment of infection. Here we did the first transcriptional profiling of purified merozoites throughout development inside the schizont and after egress. We find that merozoites within the schizont, activate a series of tightly regulated gene expression programs encoding the proteins required for host cell invasion and life within the host. After schizont egress, free merozoites still express some of these programs. Upon invasion, the merozoites transcriptional programs halt and ring cells have a distinct transcriptional profile. Each of the gene expression programs encodes for proteins implicated in a specific process and we provide evidence that they are regulated by specific transcription factors and chromatin accessibility as well as post-transcriptional mechanisms. Our work gains unprecedent insight into gene expression prior to and during host cell invasion and identifies potential new antimalarial targets.