Abstract
Obligate intracellular malaria parasites reside within a vacuolar compartment generated during invasion which is the principal interface between pathogen and host. To subvert their host cell and support their metabolism, these parasites coordinate a range of transport activities at this membrane interface that are critically important to parasite survival and virulence, including nutrient import, waste efflux, effector protein export, and uptake of host cell cytosol. Here, we review our current understanding of the transport mechanisms acting at the malaria parasite vacuole during the blood and liver-stages of development with a particular focus on recent advances in our understanding of effector protein translocation into the host cell by the Plasmodium Translocon of EXported proteins (PTEX) and small molecule transport by the PTEX membrane-spanning pore EXP2. Comparison to Toxoplasma gondii and other related apicomplexans is provided to highlight how similar and divergent mechanisms are employed to fulfill analogous transport activities.
Highlights
IntroductionPhylum Apicomplexa comprises a large group of obligate intracellular protozoan parasites that invade and subvert the cells of their hosts to create a niche for replication
This study found a size-dependent molecular sieving activity at the the Plasmodium berghei liver-stage PV membrane (PVM) with a cutoff of approximately 855 Da (Fura Red at 855 Da enters the parasitophorous vacuole (PV) while Calcium Orange at 1,070 Da does not), indicating that this pore might be distinct from the Toxoplasma or blood-stage P. falciparum pores [68,69]
The PVM is the major line of demarcation between most apicomplexan parasites and their host cells
Summary
Phylum Apicomplexa comprises a large group of obligate intracellular protozoan parasites that invade and subvert the cells of their hosts to create a niche for replication. These pathogens are an enduring burden in human and veterinary medicine and, in the case of malaria, have had a considerable impact on the human genome and the history of our species [1]. Life within the host intracellular milieu requires major investment to protect against host defenses and ensure a steady nutrient supply As such, these parasites are superb manipulators of the biology of their host cells [2]. We review our current understanding of the transport mechanisms operating at the host–parasite interface of the blood-stage malaria parasite and provide a comparison to analogous activities at the liver-stage and in the related parasite Toxoplasma gondii
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