Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

The parasitophorous vacuole of the blood-stage malaria parasite

Nature Reviews Microbiology volume 18, pages 379–391 (2020)Cite this article

Subjects

Abstract

The pathology of malaria is caused by infection of red blood cells with unicellular Plasmodium parasites. During blood-stage development, the parasite replicates within a membrane-bound parasitophorous vacuole. A central nexus for host–parasite interactions, this unique parasite shelter functions in nutrient acquisition, subcompartmentalization and the export of virulence factors, making its functional molecules attractive targets for the development of novel intervention strategies to combat the devastating impact of malaria. In this Review, we explore the origin, development, molecular composition and functions of the parasitophorous vacuole of Plasmodium blood stages. We also discuss the relevance of the malaria parasite’s intravacuolar lifestyle for successful erythrocyte infection and provide perspectives for future research directions in parasitophorous vacuole biology.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: The parasitophorous vacuole of the malaria parasite.
Fig. 2: Molecular transport across the parasitophorous vacuole membrane.
Fig. 3: The parasitophorous vacuole during egress.

Similar content being viewed by others

References

  1. World Health Organization. World Malaria Report 2018 (World Health Organization, 2018).

  2. Maier, A. G., Matuschewski, K., Zhang, M. & Rug, M. Plasmodium falciparum. Trends Parasitol. 35, 481–482 (2019).

    Article  PubMed  Google Scholar 

  3. Milner, D. A. Jr. Malaria pathogenesis. Cold Spring Harb. Perspect. Med. 8, a025569 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Koch, M. & Baum, J. The mechanics of malaria parasite invasion of the human erythrocyte - towards a reassessment of the host cell contribution. Cell Microbiol. 18, 319–329 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Aikawa, M., Miller, L. H., Johnson, J. & Rabbege, J. Erythrocyte entry by malarial parasites. A moving junction between erythrocyte and parasite. J. Cell Biol. 77, 72–82 (1978). This is a seminal ultrastructural study on Plasmodium invasion.

    Article  CAS  PubMed  Google Scholar 

  6. Ward, G. E., Miller, L. H. & Dvorak, J. A. The origin of parasitophorous vacuole membrane lipids in malaria-infected erythrocytes. J. Cell Sci. 106, 237–248 (1993).

    CAS  PubMed  Google Scholar 

  7. Haldar, K. & Uyetake, L. The movement of fluorescent endocytic tracers in Plasmodium falciparum infected erythrocytes. Mol. Biochem. Parasitol. 50, 161–177 (1992).

    Article  CAS  PubMed  Google Scholar 

  8. Pouvelle, B., Gormley, J. A. & Taraschi, T. F. Characterization of trafficking pathways and membrane genesis in malaria-infected erythrocytes. Mol. Biochem. Parasitol. 66, 83–96 (1994).

    Article  CAS  PubMed  Google Scholar 

  9. Mikkelsen, R. B., Kamber, M., Wadwa, K. S., Lin, P. S. & Schmidt-Ullrich, R. The role of lipids in Plasmodium falciparum invasion of erythrocytes: a coordinated biochemical and microscopic analysis. Proc. Natl Acad. Sci. USA 85, 5956–5960 (1988).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Dluzewski, A. R., Zicha, D., Dunn, G. A. & Gratzer, W. B. Origins of the parasitophorous vacuole membrane of the malaria parasite: surface area of the parasitized red cell. Eur. J. Cell Biol. 68, 446–449 (1995).

    CAS  PubMed  Google Scholar 

  11. Suss-Toby, E., Zimmerberg, J. & Ward, G. E. Toxoplasma invasion: the parasitophorous vacuole is formed from host cell plasma membrane and pinches off via a fission pore. Proc. Natl Acad. Sci. USA 93, 8413–8418 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Miller, L. H., Aikawa, M., Johnson, J. G. & Shiroishi, T. Interaction between cytochalasin B-treated malarial parasites and erythrocytes. Attachment junction formation. J. Exp. Med. 149, 172–184 (1979).

    Article  CAS  PubMed  Google Scholar 

  13. Håkansson, S., Charron, A. J. & Sibley, L. D. Toxoplasma evacuoles: a two-step process of secretion and fusion forms the parasitophorous vacuole. EMBO J. 20, 3132–3144 (2001).

    Article  PubMed  PubMed Central  Google Scholar 

  14. Riglar, D. T. et al. Super-resolution dissection of coordinated events during malaria parasite invasion of the human erythrocyte. Cell Host Microbe 9, 9–20 (2011).

    Article  CAS  PubMed  Google Scholar 

  15. Bannister, L. H., Mitchell, G. H., Butcher, G. A. & Dennis, E. D. Lamellar membranes associated with rhoptries in erythrocytic merozoites of Plasmodium knowlesi: a clue to the mechanism of invasion. Parasitology 92, 291–303 (1986). This study provides ultrastructural evidence for merozoite lipid secretion during invasion.

    Article  PubMed  Google Scholar 

  16. Bannister, L. H. & Mitchell, G. H. The fine structure of secretion by Plasmodium knowlesi merozoites during red cell invasion. J. Protozool. 36, 362–367 (1989).

    Article  CAS  PubMed  Google Scholar 

  17. Dluzewski, A. R., Fryer, P. R., Griffiths, S., Wilson, R. J. & Gratzer, W. B. Red cell membrane protein distribution during malarial invasion. J. Cell Sci. 92 (Pt 4), 691–699 (1989).

    PubMed  Google Scholar 

  18. Hanssen, E. et al. Electron tomography of Plasmodium falciparum merozoites reveals core cellular events that underpin erythrocyte invasion. Cell Microbiol. 15, 1457–1472 (2013).

    Article  CAS  PubMed  Google Scholar 

  19. McLaren, D. J., Bannister, L. H., Trigg, P. I. & Butcher, G. A. Freeze fracture studies on the interaction between the malaria parasite and the host erythrocyte in Plasmodium knowlesi infections. Parasitology 79, 125–139 (1979).

    Article  CAS  PubMed  Google Scholar 

  20. Lauer, S. et al. Vacuolar uptake of host components, and a role for cholesterol and sphingomyelin in malarial infection. EMBO J. 19, 3556–3564 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Murphy, S. C. et al. Erythrocyte detergent-resistant membrane proteins: their characterization and selective uptake during malarial infection. Blood 103, 1920–1928 (2004).

    Article  CAS  PubMed  Google Scholar 

  22. Mordue, D. G., Desai, N., Dustin, M. & Sibley, L. D. Invasion by Toxoplasma gondii establishes a moving junction that selectively excludes host cell plasma membrane proteins on the basis of their membrane anchoring. J. Exp. Med. 190, 1783–1792 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Torii, M., Adams, J. H., Miller, L. H. & Aikawa, M. Release of merozoite dense granules during erythrocyte invasion by Plasmodium knowlesi. Infect. Immun. 57, 3230–3233 (1989).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Culvenor, J. G., Day, K. P. & Anders, R. F. Plasmodium falciparum ring-infected erythrocyte surface antigen is released from merozoite dense granules after erythrocyte invasion. Infect. Immun. 59, 1183–1187 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Bullen, H. E. et al. Biosynthesis, localization, and macromolecular arrangement of the Plasmodium falciparum translocon of exported proteins (PTEX). J. Biol. Chem. 287, 7871–7884 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Waller, R. F., Reed, M. B., Cowman, A. F. & McFadden, G. I. Protein trafficking to the plastid of Plasmodium falciparum is via the secretory pathway. EMBO J. 19, 1794–1802 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Adisa, A. et al. The signal sequence of exported protein-1 directs the green fluorescent protein to the parasitophorous vacuole of transfected malaria parasites. J. Biol. Chem. 278, 6532–6542 (2003). This article explores the subcompartmentalization of the Plasmodium parasitophorous vacuole.

    Article  CAS  PubMed  Google Scholar 

  28. Sherling, E. S. & van Ooij, C. Host cell remodeling by pathogens: the exomembrane system in Plasmodium-infected erythrocytes. FEMS Microbiol. Rev. 40, 701–721 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Rudzinska, M. A. & Trager, W. Intracellular phagotrophy by malaria parasites: an electron microscope study of Plasmodium lophurae. J. Protozool. 4, 190–199 (1957). To our knowledge, this study is the first to acknowledge the parasitophorous vacuole by describing a double plasma membrane surrounding the parasite.

    Article  Google Scholar 

  30. Mesén-Ramírez, P. et al. Stable translocation intermediates jam global protein export in Plasmodium falciparum parasites and link the PTEX component EXP2 with translocation activity. PLoS Pathog. 12, e1005618 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Kara, U. A., Stenzel, D. J., Ingram, L. T. & Kidson, C. The parasitophorous vacuole membrane of Plasmodium falciparum: demonstration of vesicle formation using an immunoprobe. Eur. J. Cell Biol. 46, 9–17 (1988).

    CAS  PubMed  Google Scholar 

  32. Stenzel, D. J. & Kara, U. A. Sorting of malarial antigens into vesicular compartments within the host cell cytoplasm as demonstrated by immunoelectron microscopy. Eur. J. Cell Biol. 49, 311–318 (1989).

    CAS  PubMed  Google Scholar 

  33. Pouvelle, B. et al. Direct access to serum macromolecules by intraerythrocytic malaria parasites. Nature 353, 73–75 (1991).

    Article  CAS  PubMed  Google Scholar 

  34. Elmendorf, H. G. & Haldar, K. Plasmodium falciparum exports the Golgi marker sphingomyelin synthase into a tubovesicular network in the cytoplasm of mature erythrocytes. J. Cell Biol. 124, 449–462 (1994).

    Article  CAS  PubMed  Google Scholar 

  35. Behari, R. & Haldar, K. Plasmodium falciparum: protein localization along a novel, lipid-rich tubovesicular membrane network in infected erythrocytes. Exp. Parasitol. 79, 250–259 (1994).

    Article  CAS  PubMed  Google Scholar 

  36. Hanssen, E. et al. Whole cell imaging reveals novel modular features of the exomembrane system of the malaria parasite, Plasmodium falciparum. Int. J. Parasitol. 40, 123–134 (2010).

    Article  CAS  PubMed  Google Scholar 

  37. Wickert, H. et al. Evidence for trafficking of Pf EMP1 to the surface of P. falciparum-infected erythrocytes via a complex membrane network. Eur. J. Cell Biol. 82, 271–284 (2003).

    Article  CAS  PubMed  Google Scholar 

  38. Matz, J. M. et al. The Plasmodium berghei translocon of exported proteins reveals spatiotemporal dynamics of tubular extensions. Sci. Rep. 5, 12532 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Elford, B. C., Cowan, G. M. & Ferguson, D. J. Parasite-regulated membrane transport processes and metabolic control in malaria-infected erythrocytes. Biochem. J. 308, 361–374 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Grüring, C. et al. Development and host cell modifications of Plasmodium falciparum blood stages in four dimensions. Nat. Commun. 2, 165 (2011).

    Article  CAS  PubMed  Google Scholar 

  41. Kono, M. et al. Pellicle formation in the malaria parasite. J. Cell Sci. 129, 673–680 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. van Ooij, C. et al. The malaria secretome: from algorithms to essential function in blood stage infection. PLoS Pathog. 4, e1000084 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Baumeister, S. et al. Evidence for the involvement of Plasmodium falciparum proteins in the formation of new permeability pathways in the erythrocyte membrane. Mol. Microbiol. 60, 493–504 (2006).

    Article  CAS  PubMed  Google Scholar 

  44. Ginsburg, H., Krugliak, M., Eidelman, O. & Cabantchik, Z. I. New permeability pathways induced in membranes of Plasmodium falciparum infected erythrocytes. Mol. Biochem. Parasitol. 8, 177–190 (1983). This is the first report of the parasite-induced new permeability pathways.

    Article  CAS  PubMed  Google Scholar 

  45. Maier, A. G., Cooke, B. M., Cowman, A. F. & Tilley, L. Malaria parasite proteins that remodel the host erythrocyte. Nat. Rev. Microbiol. 7, 341–354 (2009).

    Article  CAS  PubMed  Google Scholar 

  46. Wahlgren, M., Goel, S. & Akhouri, R. R. Variant surface antigens of Plasmodium falciparum and their roles in severe malaria. Nat. Rev. Microbiol. 15, 479–491 (2017).

    Article  CAS  PubMed  Google Scholar 

  47. Marapana, D. S. et al. Plasmepsin V cleaves malaria effector proteins in a distinct endoplasmic reticulum translocation interactome for export to the erythrocyte. Nat. Microbiol. 3, 1010–1022 (2018).

    Article  CAS  PubMed  Google Scholar 

  48. Hiller, N. L. et al. A host-targeting signal in virulence proteins reveals a secretome in malarial infection. Science 306, 1934–1937 (2004).

    Article  CAS  PubMed  Google Scholar 

  49. Marti, M., Good, R. T., Rug, M., Knuepfer, E. & Cowman, A. F. Targeting malaria virulence and remodeling proteins to the host erythrocyte. Science 306, 1930–1933 (2004).

    Article  CAS  PubMed  Google Scholar 

  50. Boddey, J. A. et al. An aspartyl protease directs malaria effector proteins to the host cell. Nature 463, 627–631 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Russo, I. et al. Plasmepsin V licenses Plasmodium proteins for export into the host erythrocyte. Nature 463, 632–636 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Chang, H. H. et al. N-terminal processing of proteins exported by malaria parasites. Mol. Biochem. Parasitol. 160, 107–115 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Thavayogarajah, T. et al. Alternative protein secretion in the malaria parasite Plasmodium falciparum. PLoS One 10, e0125191 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Heiber, A. et al. Identification of new PNEPs indicates a substantial non-PEXEL exportome and underpins common features in Plasmodium falciparum protein export. PLoS Pathog. 9, e1003546 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Grüring, C. et al. Uncovering common principles in protein export of malaria parasites. Cell Host Microbe 12, 717–729 (2012).

    Article  CAS  PubMed  Google Scholar 

  56. Beck, J. R., Muralidharan, V., Oksman, A. & Goldberg, D. E. PTEX component HSP101 mediates export of diverse malaria effectors into host erythrocytes. Nature 511, 592–595 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Elsworth, B. et al. PTEX is an essential nexus for protein export in malaria parasites. Nature 511, 587–591 (2014).

    Article  CAS  PubMed  Google Scholar 

  58. Ansorge, I., Benting, J., Bhakdi, S. & Lingelbach, K. Protein sorting in Plasmodium falciparum-infected red blood cells permeabilized with the pore-forming protein streptolysin O. Biochem. J. 315, 307–314 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Gehde, N. et al. Protein unfolding is an essential requirement for transport across the parasitophorous vacuolar membrane of Plasmodium falciparum. Mol. Microbiol. 71, 613–628 (2009).

    Article  CAS  PubMed  Google Scholar 

  60. de Koning-Ward, T. F. et al. A newly discovered protein export machine in malaria parasites. Nature 459, 945–949 (2009). This study identified PTEX as a potential protein export translocon.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Weibezahn, J. et al. Thermotolerance requires refolding of aggregated proteins by substrate translocation through the central pore of ClpB. Cell 119, 653–665 (2004).

    Article  CAS  PubMed  Google Scholar 

  62. Charnaud, S. C., Kumarasingha, R., Bullen, H. E., Crabb, B. S. & Gilson, P. R. Knockdown of the translocon protein EXP2 in Plasmodium falciparum reduces growth and protein export. PLoS One 13, e0204785 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Garten, M. et al. EXP2 is a nutrient-permeable channel in the vacuolar membrane of Plasmodium and is essential for protein export via PTEX. Nat. Microbiol. 3, 1090–1098 (2018). This article proves that EXP2 constitutes the PVM-resident nutrient pore.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Ho, C. M. et al. Malaria parasite translocon structure and mechanism of effector export. Nature 561, 70–75 (2018). This cryo-electron microscopy study explores the 3D architecture of the PTEX translocon.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Cooney, I. et al. Structure of the Cdc48 segregase in the act of unfolding an authentic substrate. Science 365, 502–505 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Chisholm, S. A. et al. The malaria PTEX component PTEX88 interacts most closely with HSP101 at the host-parasite interface. FEBS J. 285, 2037–2055 (2018).

    Article  CAS  PubMed  Google Scholar 

  67. Chisholm, S. A. et al. Contrasting inducible knockdown of the auxiliary PTEX component PTEX88 in P. falciparum and P. berghei unmasks a role in parasite virulence. PLoS One 11, e0149296 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Matz, J. M. et al. In vivo function of PTEX88 in malaria parasite sequestration and virulence. Eukaryot. Cell 14, 528–534 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Matz, J. M., Matuschewski, K. & Kooij, T. W. Two putative protein export regulators promote Plasmodium blood stage development in vivo. Mol. Biochem. Parasitol. 191, 44–52 (2013).

    Article  CAS  PubMed  Google Scholar 

  70. Matz, J. M. & Matuschewski, K. An in silico down-scaling approach uncovers novel constituents of the Plasmodium-containing vacuole. Sci. Rep. 8, 14055 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Batinovic, S. et al. An exported protein-interacting complex involved in the trafficking of virulence determinants in Plasmodium-infected erythrocytes. Nat. Commun. 8, 16044 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Elsworth, B. et al. Proteomic analysis reveals novel proteins associated with the Plasmodium protein exporter PTEX and a loss of complex stability upon truncation of the core PTEX component, PTEX150. Cell Microbiol. 18, 1551–1569 (2016).

    Article  CAS  PubMed  Google Scholar 

  73. Matthews, K. et al. The Plasmodium translocon of exported proteins (PTEX) component thioredoxin-2 is important for maintaining normal blood-stage growth. Mol. Microbiol. 89, 1167–1186 (2013).

    Article  CAS  PubMed  Google Scholar 

  74. Kehr, S., Sturm, N., Rahlfs, S., Przyborski, J. M. & Becker, K. Compartmentation of redox metabolism in malaria parasites. PLoS Pathog. 6, e1001242 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Sharma, A., Sharma, A., Dixit, S. & Sharma, A. Structural insights into thioredoxin-2: a component of malaria parasite protein secretion machinery. Sci. Rep. 1, 179 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Boucher, I. W. et al. Structural and biochemical characterization of a mitochondrial peroxiredoxin from Plasmodium falciparum. Mol. Microbiol. 61, 948–959 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Matthews, K. M., Kalanon, M. & de Koning-Ward, T. F. Uncoupling the threading and unfoldase actions of Plasmodium HSP101 reveals differences in export between soluble and insoluble proteins. MBio 10, e01106-19 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  78. Tribensky, A., Graf, A. W., Diehl, M., Fleck, W. & Przyborski, J. M. Trafficking of PfExp1 to the parasitophorous vacuolar membrane of Plasmodium falciparum is independent of protein folding and the PTEX translocon. Cell Microbiol. 19, e12710 (2017).

    Article  CAS  Google Scholar 

  79. Pesce, E. R. & Blatch, G. L. Plasmodial Hsp40 and Hsp70 chaperones: current and future perspectives. Parasitology 141, 1167–1176 (2014).

    Article  CAS  PubMed  Google Scholar 

  80. Daniyan, M. O., Przyborski, J. M. & Shonhai, A. Partners in mischief: functional networks of heat shock proteins of Plasmodium falciparum and their influence on parasite virulence. Biomolecules 9, E295 (2019).

    Article  CAS  PubMed  Google Scholar 

  81. Banumathy, G., Singh, V. & Tatu, U. Host chaperones are recruited in membrane-bound complexes by Plasmodium falciparum. J. Biol. Chem. 277, 3902–3912 (2002).

    Article  CAS  PubMed  Google Scholar 

  82. Klemba, M., Gluzman, I. & Goldberg, D. E. A Plasmodium falciparum dipeptidyl aminopeptidase I participates in vacuolar hemoglobin degradation. J. Biol. Chem. 279, 43000–43007 (2004).

    Article  CAS  PubMed  Google Scholar 

  83. Jani, D. et al. HDP-a novel heme detoxification protein from the malaria parasite. PLoS Pathog. 4, e1000053 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Cheresh, P., Harrison, T., Fujioka, H. & Haldar, K. Targeting the malarial plastid via the parasitophorous vacuole. J. Biol. Chem. 277, 16265–16277 (2002).

    Article  CAS  PubMed  Google Scholar 

  85. Liu, J., Istvan, E. S., Gluzman, I. Y., Gross, J. & Goldberg, D. E. Plasmodium falciparum ensures its amino acid supply with multiple acquisition pathways and redundant proteolytic enzyme systems. Proc. Natl Acad. Sci. USA 103, 8840–8845 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Baumeister, S., Winterberg, M., Przyborski, J. M. & Lingelbach, K. The malaria parasite Plasmodium falciparum: cell biological peculiarities and nutritional consequences. Protoplasma 240, 3–12 (2010).

    Article  PubMed  Google Scholar 

  87. Desai, S. A., Krogstad, D. J. & McCleskey, E. W. A nutrient-permeable channel on the intraerythrocytic malaria parasite. Nature 362, 643–646 (1993). This is the first report of a PVM-resident nutrient pore in Plasmodium parasites.

    Article  CAS  PubMed  Google Scholar 

  88. Desai, S. A. & Rosenberg, R. L. Pore size of the malaria parasite’s nutrient channel. Proc. Natl Acad. Sci. USA 94, 2045–2049 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Bano, N., Romano, J. D., Jayabalasingham, B. & Coppens, I. Cellular interactions of Plasmodium liver stage with its host mammalian cell. Int. J. Parasitol. 37, 1329–1341 (2007).

    Article  CAS  PubMed  Google Scholar 

  90. Schwab, J. C., Beckers, C. J. & Joiner, K. A. The parasitophorous vacuole membrane surrounding intracellular Toxoplasma gondii functions as a molecular sieve. Proc. Natl Acad. Sci. USA 91, 509–513 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Gold, D. A. et al. The Toxoplasma dense granule proteins GRA17 and GRA23 mediate the movement of small molecules between the host and the parasitophorous vacuole. Cell Host Microbe 17, 642–652 (2015). This study explores the molecular basis of nutrient permeation across the PVM of Toxoplasma and Plasmodium parasites.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Riglar, D. T. et al. Spatial association with PTEX complexes defines regions for effector export into Plasmodium falciparum-infected erythrocytes. Nat. Commun. 4, 1415 (2013).

    Article  CAS  PubMed  Google Scholar 

  93. Low, L. M. et al. Deletion of Plasmodium falciparum protein RON3 affects the functional translocation of exported proteins and glucose uptake. MBio 10, e01460–19 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Lauer, S. A., Rathod, P. K., Ghori, N. & Haldar, K. A membrane network for nutrient import in red cells infected with the malaria parasite. Science 276, 1122–1125 (1997).

    Article  CAS  PubMed  Google Scholar 

  95. Spielmann, T., Gardiner, D. L., Beck, H. P., Trenholme, K. R. & Kemp, D. J. Organization of ETRAMPs and EXP-1 at the parasite-host cell interface of malaria parasites. Mol. Microbiol. 59, 779–794 (2006).

    Article  CAS  PubMed  Google Scholar 

  96. Wickham, M. E. et al. Trafficking and assembly of the cytoadherence complex in Plasmodium falciparum-infected human erythrocytes. EMBO J. 20, 5636–5649 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Mesén-Ramírez, P. et al. EXP1 is critical for nutrient uptake across the parasitophorous vacuole membrane of malaria parasites. PLoS Biol. 17, e3000473 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Charnaud, S. C. et al. Spatial organization of protein export in malaria parasite blood stages. Traffic 19, 605–623 (2018). This paper describes the trapping of translocation-incompetent export cargo in TVN loops.

    Article  CAS  PubMed  Google Scholar 

  99. McMillan, P. J. et al. Spatial and temporal mapping of the PfEMP1 export pathway in Plasmodium falciparum. Cell Microbiol. 15, 1401–1418 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Meibalan, E. et al. Host erythrocyte environment influences the localization of exported protein 2, an essential component of the Plasmodium translocon. Eukaryot. Cell 14, 371–384 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Kanjee, U., Rangel, G. W., Clark, M. A. & Duraisingh, M. T. Molecular and cellular interactions defining the tropism of Plasmodium vivax for reticulocytes. Curr. Opin. Microbiol. 46, 109–115 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Tilley, L., Sougrat, R., Lithgow, T. & Hanssen, E. The twists and turns of Maurer’s cleft trafficking in P. falciparum-infected erythrocytes. Traffic 9, 187–197 (2008).

    Article  CAS  PubMed  Google Scholar 

  103. Mundwiler-Pachlatko, E. & Beck, H. P. Maurer’s clefts, the enigma of Plasmodium falciparum. Proc. Natl Acad. Sci. USA 110, 19987–19994 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Clavijo, C. A., Mora, C. A. & Winograd, E. Identification of novel membrane structures in Plasmodium falciparum infected erythrocytes. Mem. Inst. Oswaldo Cruz 93, 115–120 (1998).

    Article  CAS  PubMed  Google Scholar 

  105. Langreth, S. G., Jensen, J. B., Reese, R. T. & Trager, W. Fine structure of human malaria in vitro. J. Protozool. 25, 443–452 (1978).

    Article  CAS  PubMed  Google Scholar 

  106. Glushakova, S. et al. New stages in the program of malaria parasite egress imaged in normal and sickle erythrocytes. Curr. Biol. 20, 1117–1121 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Glushakova, S., Mazar, J., Hohmann-Marriott, M. F., Hama, E. & Zimmerberg, J. Irreversible effect of cysteine protease inhibitors on the release of malaria parasites from infected erythrocytes. Cell Microbiol. 11, 95–105 (2009).

    Article  CAS  PubMed  Google Scholar 

  108. Culvenor, J. G. & Crewther, P. E. S-antigen localization in the erythrocytic stages of Plasmodium falciparum. J. Protozool. 37, 59–65 (1990).

    Article  CAS  PubMed  Google Scholar 

  109. Wickham, M. E., Culvenor, J. G. & Cowman, A. F. Selective inhibition of a two-step egress of malaria parasites from the host erythrocyte. J. Biol. Chem. 278, 37658–37663 (2003). This paper provides compelling evidence for an inside-out mode of parasite egress.

    Article  CAS  PubMed  Google Scholar 

  110. Andreadaki, M. et al. Sequential membrane rupture and vesiculation during Plasmodium berghei gametocyte egress from the red blood cell. Sci. Rep. 8, 3543 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Sologub, L. et al. Malaria proteases mediate inside-out egress of gametocytes from red blood cells following parasite transmission to the mosquito. Cell Microbiol. 13, 897–912 (2011).

    Article  CAS  PubMed  Google Scholar 

  112. Blackman, M. J. Malarial proteases and host cell egress: an ‘emerging’ cascade. Cell Microbiol. 10, 1925–1934 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Singh, S. & Chitnis, C. E. Molecular signaling involved in entry and exit of malaria parasites from host erythrocytes. Cold Spring Harb. Perspect. Med. 7, a026815 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  114. Wirth, C. C. & Pradel, G. Molecular mechanisms of host cell egress by malaria parasites. Int. J. Med. Microbiol. 302, 172–178 (2012).

    Article  CAS  PubMed  Google Scholar 

  115. Collins, C. R. et al. Malaria parasite cGMP-dependent protein kinase regulates blood stage merozoite secretory organelle discharge and egress. PLoS Pathog. 9, e1003344 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Absalon, S. et al. Calcium-dependent protein kinase 5 is required for release of egress-specific organelles in Plasmodium falciparum. MBio 9, e00130-18 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  117. Dvorin, J. D. et al. A plant-like kinase in Plasmodium falciparum regulates parasite egress from erythrocytes. Science 328, 910–912 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Arastu-Kapur, S. et al. Identification of proteases that regulate erythrocyte rupture by the malaria parasite Plasmodium falciparum. Nat. Chem. Biol. 4, 203–213 (2008).

    Article  CAS  PubMed  Google Scholar 

  119. Das, S. et al. Processing of Plasmodium falciparum merozoite surface protein MSP1 activates a spectrin-binding function enabling parasite egress from RBCs. Cell Host Microbe 18, 433–444 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Koussis, K. et al. A multifunctional serine protease primes the malaria parasite for red blood cell invasion. EMBO J. 28, 725–735 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Ruecker, A. et al. Proteolytic activation of the essential parasitophorous vacuole cysteine protease SERA6 accompanies malaria parasite egress from its host erythrocyte. J. Biol. Chem. 287, 37949–37963 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Silmon de Monerri, N. C. et al. Global identification of multiple substrates for Plasmodium falciparum SUB1, an essential malarial processing protease. Infect. Immun. 79, 1086–1097 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Yeoh, S. et al. Subcellular discharge of a serine protease mediates release of invasive malaria parasites from host erythrocytes. Cell 131, 1072–1083 (2007).

    Article  CAS  PubMed  Google Scholar 

  124. Collins, C. R., Hackett, F., Atid, J., Tan, M. S. Y. & Blackman, M. J. The Plasmodium falciparum pseudoprotease SERA5 regulates the kinetics and efficiency of malaria parasite egress from host erythrocytes. PLoS Pathog. 13, e1006453 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Pino, P. et al. A multistage antimalarial targets the plasmepsins IX and X essential for invasion and egress. Science 358, 522–528 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Nasamu, A. S. et al. Plasmepsins IX and X are essential and druggable mediators of malaria parasite egress and invasion. Science 358, 518–522 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Hale, V. L. et al. Parasitophorous vacuole poration precedes its rupture and rapid host erythrocyte cytoskeleton collapse in Plasmodium falciparum egress. Proc. Natl Acad. Sci. USA 114, 3439–3444 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Taylor, H. M. et al. The malaria parasite cyclic GMP-dependent protein kinase plays a central role in blood-stage schizogony. Eukaryot. Cell 9, 37–45 (2010).

    Article  CAS  PubMed  Google Scholar 

  129. Thomas, J. A. et al. A protease cascade regulates release of the human malaria parasite Plasmodium falciparum from host red blood cells. Nat. Microbiol. 3, 447–455 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Glushakova, S., Yin, D., Li, T. & Zimmerberg, J. Membrane transformation during malaria parasite release from human red blood cells. Curr. Biol. 15, 1645–1650 (2005).

    Article  CAS  PubMed  Google Scholar 

  131. Glushakova, S. et al. Rounding precedes rupture and breakdown of vacuolar membranes minutes before malaria parasite egress from erythrocytes. Cell Microbiol. 20, e12868 (2018). This study offers a detailed temporal dissection of vacuolar morphology during egress.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Soni, S. et al. Characterization of events preceding the release of malaria parasite from the host red blood cell. Blood Cell Mol. Dis. 35, 201–211 (2005).

    Article  CAS  Google Scholar 

  133. Burda, P. C. et al. A Plasmodium phospholipase is involved in disruption of the liver stage parasitophorous vacuole membrane. PLoS Pathog. 11, e1004760 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Sturm, A. et al. Alteration of the parasite plasma membrane and the parasitophorous vacuole membrane during exo-erythrocytic development of malaria parasites. Protist 160, 51–63 (2009).

    Article  PubMed  Google Scholar 

  135. Schmidt-Christensen, A., Sturm, A., Horstmann, S. & Heussler, V. T. Expression and processing of Plasmodium berghei SERA3 during liver stages. Cell Microbiol. 10, 1723–1734 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Kafsack, B. F. et al. Rapid membrane disruption by a perforin-like protein facilitates parasite exit from host cells. Science 323, 530–533 (2009).

    Article  CAS  PubMed  Google Scholar 

  137. Pszenny, V. et al. A lipolytic lecithin:cholesterol acyltransferase secreted by Toxoplasma facilitates parasite replication and egress. J. Biol. Chem. 291, 3725–3746 (2016).

    Article  CAS  PubMed  Google Scholar 

  138. Wirth, C. C., Bennink, S., Scheuermayer, M., Fischer, R. & Pradel, G. Perforin-like protein PPLP4 is crucial for mosquito midgut infection by Plasmodium falciparum. Mol. Biochem. Parasitol. 201, 90–99 (2015).

    Article  CAS  PubMed  Google Scholar 

  139. Tavares, J., Amino, R. & Menard, R. The role of MACPF proteins in the biology of malaria and other apicomplexan parasites. Subcell. Biochem. 80, 241–253 (2014).

    Article  CAS  PubMed  Google Scholar 

  140. Yang, A. S. P. et al. Cell traversal activity is important for Plasmodium falciparum liver infection in humanized mice. Cell Rep. 18, 3105–3116 (2017).

    Article  CAS  PubMed  Google Scholar 

  141. Flammersfeld, A., Lang, C., Flieger, A. & Pradel, G. Phospholipases during membrane dynamics in malaria parasites. Int. J. Med. Microbiol. 308, 129–141 (2018).

    Article  CAS  PubMed  Google Scholar 

  142. Kumar, Y. & Valdivia, R. H. Leading a sheltered life: intracellular pathogens and maintenance of vacuolar compartments. Cell Host Microbe 5, 593–601 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Martens, S. et al. Disruption of Toxoplasma gondii parasitophorous vacuoles by the mouse p47-resistance GTPases. PLoS Pathog. 1, e24 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Asada, M. et al. Gliding motility of Babesia bovis merozoites visualized by time-lapse video microscopy. PLoS One 7, e35227 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Rudzinska, M. A., Trager, W., Lewengrub, S. J. & Gubert, E. An electron microscopic study of Babesia microti invading erythrocytes. Cell Tissue Res. 169, 323–334 (1976).

    Article  CAS  PubMed  Google Scholar 

  146. Shaw, M. K. & Tilney, L. G. The entry of Theileria parva merozoites into bovine erythrocytes occurs by a process similar to sporozoite invasion of lymphocytes. Parasitology 111, 455–461 (1995).

    Article  PubMed  Google Scholar 

  147. Gohil, S., Kats, L. M., Sturm, A. & Cooke, B. M. Recent insights into alteration of red blood cells by Babesia bovis: moovin’ forward. Trends Parasitol. 26, 591–599 (2010).

    Article  PubMed  Google Scholar 

  148. Hutchings, C. L. et al. New insights into the altered adhesive and mechanical properties of red blood cells parasitized by Babesia bovis. Mol. Microbiol. 65, 1092–1105 (2007).

    Article  CAS  PubMed  Google Scholar 

  149. Pellé, K. G. et al. Shared elements of host-targeting pathways among apicomplexan parasites of differing lifestyles. Cell Microbiol. 17, 1618–1639 (2015).

    Article  CAS  PubMed  Google Scholar 

  150. Edwards, C. J. & Fuller, J. Oxidative stress in erythrocytes. Comp. Haematol. Int. 6, 24–31 (1996).

    Article  CAS  Google Scholar 

  151. Aich, A., Freundlich, M. & Vekilov, P. G. The free heme concentration in healthy human erythrocytes. Blood Cell Mol. Dis. 55, 402–409 (2015).

    Article  CAS  Google Scholar 

  152. Cimen, M. Y. Free radical metabolism in human erythrocytes. Clin. Chim. Acta 390, 1–11 (2008).

    Article  CAS  PubMed  Google Scholar 

  153. Lisewski, A. M. et al. Supergenomic network compression and the discovery of EXP1 as a glutathione transferase inhibited by artesunate. Cell 158, 916–928 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. van Dijk, M. R. et al. Genetically attenuated, P36p-deficient malarial sporozoites induce protective immunity and apoptosis of infected liver cells. Proc. Natl Acad. Sci. USA 102, 12194–12199 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Annoura, T. et al. Two Plasmodium 6-Cys family-related proteins have distinct and critical roles in liver-stage development. FASEB J. 28, 2158–2170 (2014).

    Article  CAS  PubMed  Google Scholar 

  156. Ploemen, I. H. et al. Plasmodium berghei Δp52&p36 parasites develop independent of a parasitophorous vacuole membrane in Huh-7 liver cells. PLoS One 7, e50772 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Trager, W. & Williams, J. Extracellular (axenic) development in vitro of the erythrocytic cycle of Plasmodium falciparum. Proc. Natl Acad. Sci. USA 89, 5351–5355 (1992). This study reports on the development of P. falciparum in an axenic culture system.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Schnider, C. B., Bausch-Fluck, D., Bruhlmann, F., Heussler, V. T. & Burda, P. C. BioID reveals novel proteins of the Plasmodium parasitophorous vacuole membrane. mSphere 3, e00522–17 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Khosh-Naucke, M. et al. Identification of novel parasitophorous vacuole proteins in P. falciparum parasites using BioID. Int. J. Med. Microbiol. 308, 13–24 (2018).

    Article  CAS  PubMed  Google Scholar 

  160. Li, J., Mitamura, T., Fox, B. A., Bzik, D. J. & Horii, T. Differential localization of processed fragments of Plasmodium falciparum serine repeat antigen and further processing of its N-terminal 47 kDa fragment. Parasitol. Int. 51, 343–352 (2002).

    Article  CAS  PubMed  Google Scholar 

  161. Wickert, H. & Krohne, G. The complex morphology of Maurer’s clefts: from discovery to three-dimensional reconstructions. Trends Parasitol. 23, 502–509 (2007).

    Article  PubMed  Google Scholar 

  162. Spycher, C. et al. Genesis of and trafficking to the Maurer’s clefts of Plasmodium falciparum-infected erythrocytes. Mol. Cell Biol. 26, 4074–4085 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. Wickert, H., Gottler, W., Krohne, G. & Lanzer, M. Maurer’s cleft organization in the cytoplasm of Plasmodium falciparum-infected erythrocytes: new insights from three-dimensional reconstruction of serial ultrathin sections. Eur. J. Cell Biol. 83, 567–582 (2004).

    Article  PubMed  Google Scholar 

  164. Hanssen, E. et al. Targeted mutagenesis of the ring-exported protein-1 of Plasmodium falciparum disrupts the architecture of Maurer’s cleft organelles. Mol. Microbiol. 69, 938–953 (2008).

    Article  CAS  PubMed  Google Scholar 

  165. Nyalwidhe, J. & Lingelbach, K. Proteases and chaperones are the most abundant proteins in the parasitophorous vacuole of Plasmodium falciparum-infected erythrocytes. Proteomics 6, 1563–1573 (2006). This is the first published attempt to identify parasitophorous vacuole matrix proteins using differential biotin labelling.

    Article  CAS  PubMed  Google Scholar 

  166. Jackson, K. E. et al. Selective permeabilization of the host cell membrane of Plasmodium falciparum-infected red blood cells with streptolysin O and equinatoxin II. Biochem. J. 403, 167–175 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Siau, A., Huang, X., Weng, M., Sze, S. K. & Preiser, P. R. Proteome mapping of Plasmodium: identification of the P. yoelii remodellome. Sci. Rep. 6, 31055 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Burghaus, P. A. & Lingelbach, K. Luciferase, when fused to an N-terminal signal peptide, is secreted from transfected Plasmodium falciparum and transported to the cytosol of infected erythrocytes. J. Biol. Chem. 276, 26838–26845 (2001).

    Article  CAS  PubMed  Google Scholar 

  169. Bushell, E. et al. Functional profiling of a Plasmodium genome reveals an abundance of essential genes. Cell 170, 260–272 e268 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Zhang, M. et al. Uncovering the essential genes of the human malaria parasite Plasmodium falciparum by saturation mutagenesis. Science 360, eaap7847 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  171. Spielmann, T., Fergusen, D. J. & Beck, H. P. etramps, a new Plasmodium falciparum gene family coding for developmentally regulated and highly charged membrane proteins located at the parasite-host cell interface. Mol. Biol. Cell 14, 1529–1544 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors thank C. Bisson (Birkbeck College, University of London) for electron microscopy images of E64-treated P. falciparum schizonts. This work was supported in part by funding to M.J.B. and J.M.M. from the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001043), the UK Medical Research Council (FC001043) and the Wellcome Trust (FC001043). The work was also supported by National Institutes of Health grant HL133453 to J.R.B. and a stipend from the German Research Foundation (DFG; project number 419345764) to J.M.M.

Author information

Authors and Affiliations

  1. Malaria Biochemistry Laboratory, The Francis Crick Institute, London, UK

    Joachim M. Matz & Michael J. Blackman

  2. Department of Biomedical Sciences, Iowa State University, Ames, IA, USA

    Josh R. Beck

  3. Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK

    Michael J. Blackman

Authors
  1. Joachim M. Matz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Josh R. Beck
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michael J. Blackman
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed substantially to the conceptualization and writing of the manuscript. J.M.M. conceived the manuscript. The first draft was written by J.M.M. and J.R.B. with input from M.J.B. All authors edited and reviewed the manuscript before submission.

Corresponding authors

Correspondence to Joachim M. Matz or Michael J. Blackman.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Peer review information

Nature Reviews Microbiology thanks P. Gilson and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Glossary

Merozoites

The invasive parasite stages that are released during host cell egress to infect erythrocytes.

Ring stage

A young parasite stage, which marks the onset of intraerythrocytic development after invasion.

Trophozoite

Intraerythrocytic parasite stage characterized by rapid growth and biomass production.

Schizont

Intracellular parasite stage that undergoes multiple rounds of nuclear division and concerted cytokinesis to form new daughter merozoites.

Membrane capacitance

The ability of a biological membrane to store energy in the form of an electrical charge, the magnitude of which is directly proportional to the membrane surface area.

Sec translocon

Endoplasmic reticulum-resident protein complex that translocates secretory proteins from the cytoplasm across or into the endoplasmic reticulum membrane.

Signal peptide

Short N-terminal peptide of 16–30 amino acids which directs secretory proteins to the Sec translocon and which is cleaved on translocation.

Rhodamine 123

A fluorescent potentiometric dye that accumulates in mitochondria in a manner which is dependent on membrane polarization.

Haemozoin

Crystals of haemoglobin-derived haem in the parasite’s food vacuole.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Matz, J.M., Beck, J.R. & Blackman, M.J. The parasitophorous vacuole of the blood-stage malaria parasite. Nat Rev Microbiol 18, 379–391 (2020). https://doi.org/10.1038/s41579-019-0321-3

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41579-019-0321-3

This article is cited by

Search

Advanced search

Quick links

Nature Briefing Microbiology

Sign up for the Nature Briefing: Microbiology newsletter — what matters in microbiology research, free to your inbox weekly.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing: Microbiology