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Free keywords:
Plasmodium; Membrane proteins; Cell membranes; Vesicles; Cytoplasm; Red blood cells; Parasitic diseases; Plasmodium falciparum
Abstract:
Malaria is a disease caused by Plasmodium parasites that is still a leading cause of death in many low-income countries, and for which currently available therapeutic strategies are not succeeding in its control, let alone eradication. An interesting feature observed after Plasmodium invasion is the increase of extracellular vesicles (EVs) generated by parasitized red blood cells (pRBCs), which lack a vesicular trafficking that would explain EV production. Here, by combining different approaches, we demonstrated the participation of the endosomal sorting complex required for transport (ESCRT) machinery from Plasmodium falciparum in the production of EVs in pRBCs. Moreover, we were able to detect ESCRT-III proteins adjacent to the membrane of the host and in EVs purified from a pRBC culture, which shows the export of these proteins and their participation in EV production. Finally, the disruption of an ESCRT-III associated gene, Pfvps60, led to a significant reduction in the amount of EVs. Altogether, these results confirm ESCRT-III participation in EV production and provide novel information on the P. falciparum protein export mechanisms, which can be used for the development of new therapeutic strategies against malaria, based on the disruption of EV formation and trafficking.
