Investigation of membrane permeabilization during Plasmodium falciparum egress

Abstract

The exit from the red blood cell (RBC) or egress is an essential step during Plasmodium falciparum erythrocytic cycle. Egress is preceded by permeabilization of parasitophorous vacuole (PV) and host cell membranes, a process regulated by signaling pathways derived from the parasite and the red blood cell and dependent on kinases, phosphatases, proteases, perforines and molecules not yet identified. Parasite synchronization and quantification of membrane permeabilization are caveats of previous studies, which impaired the determination in which order the events occur and molecules involved. In this study, Plasmodium falciparum conditional knockout lines for the kinases PKG or CDPK5, which also express the reporter NLuc in the PV or in the RBC, will be applied so that tight synchronization prior to egress and accurate quantification of membrane permeabilization can be obtained. Such a strategy should allow the investigation of the effect of known inhibitors on egress after the activation of either PKG or CDPK5 and therefore, the identification of some of the molecules involved in a timely manner. (AU)