How the malaria parasite eats lunch

The food vacuole of Plasmodium falciparum The parasite Plasmodium falciparum is the causative agent of severe malaria in humans, killing somewhere between 600,000 and 1.2 million people each year. The complex life cycle includes an asexual proliferation within human erythrocytes, characterised by three distinct stages: rings, trophozoites and schizonts. Adaptations to the intra-erythrocytic lifestyle have created new and in some cases unique organelles, such as an endosomal/lysosomal-like organelle, the food vacuole. Haemoglobin degradation during the erythrocytic life stages is the major function of the food vacuole (FV) of Plasmodium falciparum and the target of several anti-malarial drugs that interfere with this metabolic pathway, killing the parasite. Two multi-spanning food vacuole membrane proteins are known, the multidrug resistance protein 1 (PfMDR1) and Chloroquine Resistance Transporter (PfCRT). Both modulate resistance to drugs that act in the food vacuole.

To investigate the formation and behaviour of the food vacuole membrane researchers generated inducible GFP fusions of chloroquine sensitive and resistant forms of the PfCRT protein. This inducible expression system them to follow newly-induced fusion proteins, and corroborated a previous report of a direct trafficking route from the ER/Golgi to the food vacuole membrane. These parasites also allowed the definition of a food vacuole compartment in ring stage parasites well before haemozoin crystals were apparent, as well as the elucidation of secondary PfCRT-labelled compartments adjacent to the food vacuole in late stage parasites.

In addition to previously demonstrated Brefeldin A sensitivity, the trafficking of PfCRT is disrupted by Dynasore, a non competitive inhibitor of dynamin-mediated vesicle formation. Chloroquine sensitivity was not altered in parasites over-expressing chloroquine resistant or sensitive forms of the PfCRT fused to GFP, suggesting that the PfCRT does not mediate chloroquine transport as a GFP fusion protein.

 

Investigation of the Plasmodium falciparum Food Vacuole through Inducible Expression of the Chloroquine Resistance Transporter (PfCRT). (2012) PLoS ONE 7(6): e38781. doi:10.1371/journal.pone.0038781

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