title: Electron tomography of Plasmodium falciparum merozoites reveals core cellular events that underpin erythrocyte invasion.
abstract: Erythrocyte invasion by merozoites forms of the malaria parasite is a key step in the establishment of human malaria disease. To date, efforts to understand cellular events underpinning entry have been limited to insights from non-human parasites, with no studies at sub-micrometer resolution undertaken using the most virulent human malaria parasite, Plasmodium falciparum. This leaves our understanding of the dynamics of merozoite sub-cellular compartments during infectionincomplete, in particular that of the secretory organelles. Using advances in P. falciparum merozoite isolation and new imaging techniques we present a three-dimensional study of invasion using electron microscopy, cryo-electron tomography and cryo-X-ray tomography. We describe the core architectural features of invasion and identify fusion between rhoptries at the commencement of invasion as a hitherto overlooked event that likely provides a critical step that initiates entry. Given the centrality of merozoite organelle proteins to vaccine development, these insights provide a mechanistic framework to understand therapeutic strategies targeted towards the cellular events of invasion.
authors: Advanced Microscopy Facility and Center of Excellence for Coherent X-ray Science, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Vic., 3010, Australia.
authors: Eric
authors: E
authors: Hanssen
authors: Chaitali
authors: C
authors: Dekiwadia
authors: David T
authors: DT
authors: Riglar
authors: Melanie
authors: M
authors: Rug
authors: Leandro
authors: L
authors: Lemgruber
authors: Alan F
authors: AF
authors: Cowman
authors: Marek
authors: M
authors: Cyrklaff
authors: Mikhail
authors: M
authors: Kudryashev
authors: Friedrich
authors: F
authors: Frischknecht
authors: Jake
authors: J
authors: Baum
authors: Stuart A
authors: SA
authors: Ralph
mesh_terms: D055032:Electron Microscope Tomography; D004705:Endocytosis; D004912:Erythrocytes / Q000469:parasitology* / Q000648:ultrastructure*; D054884:Host-Pathogen Interactions; D006801:Humans; D021621:Imaging, Three-Dimensional; D052940:Merozoites / Q000648:ultrastructure*; D010963:Plasmodium falciparum / Q000502:physiology* / Q000648:ultrastructure*