Role of erythrocyte membrane microdomains in Plasmodium falciparum infection

Disruption of erythrocyte membrane microdomains (MMs) prevents invasion by merozoites, suggesting an essential role of this membrane compartment in susceptibility to infection by Plasmodium falciparum. With the aim of characterizing distinct erythrocyte MM types, we performed a proteomic analysis of erythrocyte MMs purified on sucrose gradient and categorized the proteins into different groups by hierarchical cluster analysis, on the basis of their abundance along the gradient. Only 11 erythrocyte proteins have been described so far to be involved in P. falciparum invasion process. Strikingly, 8 of them were identified in our analysis and in particular 6 of them fall in the same cluster, comprising a total of 15 proteins. This result strongly suggests that a specific MM type may be involved in P. falciparum attachment and invasion. We investigated the role of the most promising candidate of the invasion cluster in P. falciparum infection by in vitro invasion assays in the presence of inhibitors. Inhibitor-treated erythrocytes were infected with P. falciparum purified schizonts and invasion rates were measured 6 hours later by FACS analysis. More than 90% parasitaemia reduction was observed in the inhibitor-treated sample, compared to the untreated control. Our results confirmed the essential role of erythrocyte MMs in P. falciparum invasion and allowed the identification of a new possible drug target in the fight against malaria.