Revisiting Putative Functional Properties of the Plasmodium falciparum Pf155/RESA Protein Using Genetically Engineered Parasites

Pf155/RESA (Ring Infected Erythrocyte Surface Antigen), is a Plasmodium falciparum protein discharged by the dense granules of merozoites during invasion and exported to the inner face of the erythrocyte membrane, where it interacts with spectrin in the young stages. Chromosome 1 subtelomeric deletion, eliminating amongst others the resa gene, may occur during adaptation of parasite isolates to in vitro culture. This is accompanied by erythrocyte membrane modifications of the red blood cell, such as increased adhesion and effect on membrane rigidity. It has been proposed that RESA was likely to contribute to these functional and rheological modifications. To assess this, we have constructed resa knock-out parasites in the FUP/CB strain. This results in negativating the erythrocyte membrane immunofluorescence of glutaraldehyde-fixed red blood cells (EMIF), indicating that RESA is critical for EMIF reactivity of hyperimmune human sera. Phenotypic and functional analysis of resa k.o. parasites indicated that loss of RESA expression neither affects membrane rigidity nor CD36 binding under flow conditions. Furthermore, infection of Saimiri sciureus monkeys showed that resa gene deletion does not account on its own for the greater adaptation and parasite virulence in this model.