The networking platform of the malaria parasite

Malaria is the most serious mosquito-borne parasitic disease, caused mainly by the intracellular parasite Plasmodium falciparum (Pf). The parasite invades human red blood cells and releases extracellular vesicles (EVs) to communicate and alter its host responses. Seeking to identify EV subpopulations, we subject malaria-derived EVs to size separation analysis, using asymmetric flow field-flow fractionation. Multi-technique analysis reveals surprising characteristics: we identify two distinct EV subpopulations differing in size and protein content. Small EVs are enriched in complement-system proteins and large EVs in proteasome subunits. Atomic force microscope imaging combined with biophysical and machine-learning methods further emphasizes the difference in mechanical and membrane fusion properties between the two subpopulations. These results shed light on the sophisticated mechanism by which malaria parasites utilize EV subpopulations as a communication tool to target different cellular destinations or host systems.