Macromolecular transport in malaria-infected erythrocytes

Abstract

Transport of macromolecules in the external medium or host cell cytosol to intracellular Plasmodium falciparum malaria parasites occurs by two distinct pathways. Macromolecules in the erythrocyte cytosol are ingested by the parasite via a specialized organelle, the cytostome, and are transported to the parasite food vacuole. By contrast, blood-stage parasites internalize macromolecules from the external medium through a pathway that bypasses the erythrocyte cytosol. We coined this pathway the 'parasitophorous duct'. Since our original report, a number of permutations of this model have been proposed. (Macro)molecules in the aqueous compartment bounded by the parasitophorous vacuole membrane (PVM) and the parasite plasma membrane are internalized by parasite fluid-phase endocytosis. Serial sections of parasites fixed and stained by various methods for transmission electron microscopy revealed areas of apparent membrane continuity between the erythrocyte membrane and the PVM, which could leave the parasites exposed to the external medium. Macromolecules up to 50-70 nm in diameter have direct access to intraerythrocytic parasites. This size exclusion is consistent with the dimensions of the parasitophorous duct pathway revealed by electron microscopy. The identification and characterization of this new pathway has stimulated investigators to pursue new areas in malaria research, including parasite transfection, antisense RNA and chemotherapy using membrane-impermeable drugs.