Malaria Biochemistry Laboratory, The Francis Crick Institute, London, United Kingdom; Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, United States
Ellen Knuepfer
Malaria Parasitology Laboratory, The Francis Crick Institute, London, United Kingdom
Joseph A Brzostowski
Laboratory of Immunogenetics Imaging Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, United States
Louis H Miller
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, United States
Malaria Biochemistry Laboratory, The Francis Crick Institute, London, United Kingdom; Department of Pathogen Molecular Biology, London School of Hygiene & Tropical Medicine, London, United Kingdom
Merozoites of the protozoan parasite responsible for the most virulent form of malaria, Plasmodium falciparum, invade erythrocytes. Invasion involves discharge of rhoptries, specialized secretory organelles. Once intracellular, parasites induce increased nutrient uptake by generating new permeability pathways (NPP) including a Plasmodium surface anion channel (PSAC). RhopH1/Clag3, one member of the three-protein RhopH complex, is important for PSAC/NPP activity. However, the roles of the other members of the RhopH complex in PSAC/NPP establishment are unknown and it is unclear whether any of the RhopH proteins play a role in invasion. Here we demonstrate that RhopH3, the smallest component of the complex, is essential for parasite survival. Conditional truncation of RhopH3 substantially reduces invasive capacity. Those mutant parasites that do invade are defective in nutrient import and die. Our results identify a dual role for RhopH3 that links erythrocyte invasion to formation of the PSAC/NPP essential for parasite survival within host erythrocytes.
