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  • Review Article
  • Published:

Plasmodium species: master renovators of their host cells

Nature Reviews Microbiology volume 14, pages 494–507 (2016)Cite this article

Subjects

Key Points

  • The capacity of Plasmodium parasites to extensively remodel the erythrocytes in which they reside is fundamental to their ability to survive within these enucleated, metabolically inactive cells and to evade the immune response of the host.

  • Plasmodium falciparum exports ∼10% of its proteome across the parasite membrane and the surrounding vacuolar membrane into a host erythrocyte.

  • Many proteins that are exported by Plasmodium parasites contain a distinct trafficking motif, the Plasmodium export element (PEXEL), that requires processing in the endoplasmic reticulum by an aspartyl protease to direct their export.

  • A unique translocon known as the Plasmodium translocon of exported proteins (PTEX) is present at the vacuolar membrane and functions as a selective gateway for proteins to access host erythrocytes.

  • As erythrocytes lack their own trafficking machinery, Plasmodium parasites establish an exomembrane trafficking system in the host erythrocyte. This system functions as a sorting depot for exported proteins and has a role in the delivery of proteins to the erythrocyte membrane.

  • The export pathway of Plasmodium parasites contains novel constituents that are not found in higher eukaryotes and hence provides potential new drug targets for combating malaria.

Abstract

Plasmodium parasites, the causative agents of malaria, have developed elaborate strategies that they use to survive and thrive within different intracellular environments. During the blood stage of infection, the parasite is a master renovator of its erythrocyte host cell, and the changes in cell morphology and function that are induced by the parasite promote survival and contribute to the pathogenesis of severe malaria. In this Review, we discuss how Plasmodium parasites use the protein trafficking motif Plasmodium export element (PEXEL), protease-mediated polypeptide processing, a novel translocon termed the Plasmodium translocon of exported proteins (PTEX) and exomembranous structures to export hundreds of proteins to discrete subcellular locations in the host erythrocytes, which enables the parasite to gain access to vital nutrients and to evade the immune defence mechanisms of the host.

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Figure 1: Overview of the Plasmodium spp. life cycle.
Figure 2: Key steps and compartments in the protein export pathway.
Figure 3: A putative model of the translocon.

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Acknowledgements

The authors apologize to those colleagues whose work could not be cited owing to length constraints. They acknowledge support from the National Health and Medical Research Council, Australia.

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Authors and Affiliations

  1. School of Medicine, Deakin University, Waurn Ponds, 3216, Victoria, Australia

    Tania F. de Koning-Ward

  2. Department of Biochemistry and Molecular Biology, Bio21 Institute, The University of Melbourne, 3010, Victoria, Australia

    Matthew W.A. Dixon & Leann Tilley

  3. Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, 3004, Victoria, Australia

    Paul R. Gilson

  4. Department of Microbiology, Monash University, Melbourne, 3800, Victoria, Australia

    Paul R. Gilson

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  1. Tania F. de Koning-Ward
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  2. Matthew W.A. Dixon
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Correspondence to Tania F. de Koning-Ward.

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Glossary

Parasitophorous vacuole

A compartment that is formed in host cells in which apicomplexan parasites reside and develop.

New permeation pathways

(NPPs). These are induced in the membrane of infected erythrocytes to enable the passage of low-molecular-weight molecules.

Rhoptry

A specialized secretory organelle that is located at the apical end of apicomplexan parasites.

Parasitophorous vacuole membrane

(PVM). The membrane that surrounds the parasitophorous vacuole that, in the case of erythrocytes, is formed through the invagination of the membrane bilayer during parasite invasion.

P. falciparum erythrocyte membrane protein 1

(PfEMP1). A major virulence factor of Plasmodium falciparum. It is a member of a family of approximately 60 proteins of which one allele is expressed in a particular parasite.

Exomembrane system

A network of membranes that, in addition to the limiting membrane of the parasite, is present in the cytoplasm of the host cell.

Exportomes

The full complement of exported proteins in malaria parasites.

Translocon

A complex of proteins that includes a membrane-spanning channel component and provides a passage for polypeptides to cross membranes.

Knobs

Electron-dense protrusions on the membrane of erythrocytes that are infected with Plasmodium falciparum and that increase the stiffness and adhesiveness of the erythrocyte.

Plasmodium export element

(PEXEL). A pentameric amino acid motif in the amino-terminal region of proteins that guides their export.

PEXEL-negative proteins

(PNEPs). Plasmodium export element (PEXEL)-negative exported proteins lack a PEXEL motif and contain a hydrophobic region that mediates entry into the secretory pathway.

Plasmepsin V

A parasite aspartyl protease that cleaves the Plasmodium export element (PEXEL) motif.

Plasmodium translocon of exported proteins

(PTEX). The Plasmodium translocon of exported proteins provides a selective gateway for parasite proteins to traverse the parasitophorous vacuole membrane and access the host erythrocyte.

Dense granules

Small vesicular bodies that are located at the apical end of the cytoplasm in the invasive form (merozoite) of the malaria parasite.

Patency

The time point during an infection when parasites are detectable.

J-dots

Proteinaceous chaperone complexes that are present in the cytoplasm of erythrocytes that are infected with Plasmodium falciparum.

Maurer's clefts

Flattened, single-membrane-bound structures that are constructed by Plasmodium falciparum in the cytoplasm of infected erythrocytes. These clefts receive exported protein cargo and deliver it to the surface of the erythrocyte.

Lamellae

Thin, plate-like membranous structures.

Cisterna

Flattened membrane disc-like structures.

Dynamins

Large GTPases that are implicated in the budding and scission of nascent vesicles from their parent membranes.

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de Koning-Ward, T., Dixon, M., Tilley, L. et al. Plasmodium species: master renovators of their host cells. Nat Rev Microbiol 14, 494–507 (2016). https://doi.org/10.1038/nrmicro.2016.79

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