THE DIGESTIVE VACUOLE OF PLASMODIUM FALCIPARUM IN PROGRAMMED CELL DEATH

Abstract

Programmed cell death (PCD) has been reported in many protozoan parasites, including a causative agent of malaria, <i>Plasmodium falciparum</i>. Previously we reported that micromolar doses of chloroquine can disrupt the digestive vacuole (DV) of <i>P. falciparum</i> and induce features reminiscent of mammalian apoptosis. Reported in this thesis is the further characterization of the dose and duration of chloroquine required to induce DV disruption and PCD features in the parasite, demonstrating that physiologically-relevant concentrations of the drug are sufficient and thereby proposing a novel mode of chloroquine action. Also presented is a high-content screen for novel compounds that disrupt the DV, as a proof-of-concept that this phenomenon is a viable strategy for drug discovery. Discussed in this thesis are the effects of DV disruption on the host red blood cell the parasite resides in, and how they impact the interactions of the parasite and the host.