Malaria parasites utilize extracellular vesicle subpopulations as a communication tool

Malaria is the most serious mosquito-borne parasitic disease, caused mainly by the intracellular parasite Plasmodium falciparum. The parasite invades human red blood cells and releases extracellular vesicles (EVs) to alter its host responses. It has become clear that EVs are generally composed of sub-populations. Seeking to identify EV subpopulations, researchers at the Weizmann Institute of Science subjected malaria-derived EVs to size-separation analysis, using asymmetric flow field-flow fractionation. Multi-technique analysis revealed surprising characteristics: two distinct EV subpopulations differing in size and protein content. Small EVs are enriched in complement-system proteins and large EVs in proteasome subunits. The researchers then measured the membrane fusion abilities of each subpopulation with three types of host cellular membranes: plasma, late and early endosome. Remarkably, small EVs fused to early endosome liposomes at significantly greater levels than large EVs. Atomic force microscope imaging combined with machine-learning methods further emphasized the difference in biophysical 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.