Plasmodium

Lawrence H Bannister, King's College London, London, UK
Irwin W Sherman, University of California, Riverside, California, USA

Published online: December 2009

DOI: 10.1002/9780470015902.a0001970.pub2

Plasmodium is a genus of parasitic protozoa which infect erythrocytes of vertebrates and cause malaria. Their life cycle alternates between mosquito and vertebrate hosts. Parasites enter the bloodstream after a mosquito bite, and multiply sequentially within liver cells and erythrocytes before becoming male or female sexual forms. When ingested by a mosquito, these fuse, then the parasite multiplies again to form more invasive stages which are transmitted back in the insect's saliva to a vertebrate. All invasive stages have specialized secretory structures (apical organelles) typical of the protozoan subphylum Apicomplexa, enabling them to invade cells and tissues. Parasites exploit erythrocytes by ingesting haemoglobin and exporting molecules which change erythrocyte membrane properties. Five species infect humans, the most lethal being Plasmodium falciparum which can cause pathology and death by clogging blood vessels in brain, viscera and placenta. Many hundreds more species infect other mammals, birds and lizards.

Key Concepts:

  • Intracellular parasitism. Many apicomplexan protozoa invade and exploit the cells of their hosts, situated in a nutrient-rich environment and protected from attack by their host's immune system.
  • Alternation of hosts. All parasites of the genus Plasmodium have two different types of host which they parasitize alternately, a vertebrate and a mosquito. This arrangement enables the parasite to multiply numbers greatly in the richly nutrient environment of the vertebrate host, and also to find new hosts via the mosquito vector.
  • The parasitophorous vacuole. Blood stage parasites are enclosed in a cavity within the erythrocyte (parasitophorous vacuole) lined by membrane (parasitophorous vacuole membrane) derived from the erythrocyte surface membrane. The parasite is therefore not in direct contact with the erythrocyte cytoplasm.
  • Life-cycle stages. The structure, molecular composition and behaviour of Plasmodium parasites change constantly throughout its life cycle, as the expression patterns of its genes vary within both vertebrates and mosquito hosts, enabling parasites to exploit different aspects of the host's biology.
  • Intracellular invasion. Intracellular life requires the ability to selectively capture and enter host cells, seen in the invasion by merozoites into erythrocytes and of sporozoites into liver hepatocytes. In both cases this depends on the secretion of adhesive proteins and membrane-altering substances by the parasite, and on its actin–myosin driven locomotion.
  • Host cell transformation. Intracellular parasites export various molecules into the host cell to transform its properties. In erythrocytes this increases permeability to nutrients and in some species causes the erythrocyte membrane to adhere to blood vessel walls. The parasite also consumes host cell cytoplasm.
  • Malaria. This is a generic name given to diseases in vertebrates caused by species of Plasmodium. They are typified in mammals by cyclic episodes of fever and may have many other complications including anaemia, spleen pathology, placental dysfunction, neurological complications and in severe malaria, coma and death.
  • Parasite evolution. Molecular studies indicate that the evolution of Plasmodium species is closely linked to the evolution of terrestrial vertebrates and has impacted significantly on the human genome.

Keywords: malaria; apicomplexa; parasite; erythrocyte; Plasmodium; protozoa

Figure 1. The main features of the life cycle of the malaria parasite Plasmodium falciparum, showing its different phases in vertebrate and mosquito hosts.
Figure 2. The stages of Plasmodium falciparum in the blood. (a) Light micrographs of infected erythrocytes stained as a blood film with Giemsa's stain are assembled into the major stages of asexual blood cycle and the sexual blood stages. (b) A transmission electron micrograph of a section through a blood sample infected with the simian malaria parasite Plasmodium knowlesi. A number of different stages are visible. To aid interpretation, false colour has been added to the monochrome micrographs, the parasites being coloured blue and the erythrocytes red. The same convention is followed in most other figures in this article. (c) An electron micrograph (EM) of a malaria merozoite, showing its main structural features. (d) Electron micrographs of the main blood stages of Plasmodium falciparum are assembled, coloured as in (b); nuclei are indicated in purple. Light micrographs of cells shown in (a) were provided by Gabriele Margos, Bath University, UK.
Figure 3. (a)–(d) The merozoite and invasion. (a) A diagram shows the main organelles typical of Plasmodium merozoites. (b) Two merozoites of Plasmodium falciparum (arrows) and two erythrocytes have been imaged by scanning electron microscopy. (c) Depicts the main steps in merozoite invasion of an erythrocyte, related in (d) to three transmission EMs of invading Plasmodium knowlesi merozoites; false colours include green for a mitochondrion and orange for an apicoplast. (d (iv)) is altered from Bannister LH, Mitchell GH, Butcher GA and Dennis ED (1986). Lamellar membranes associated with rhoptries in erythrocytic merozoites of Plasmodium knowlesi: a clue to the mechanism of invasion. Parasitology 92: 291–303, with permission of Cambridge University Press.
Figure 4. (a)–(f) Details of trophozoite and schizont organization. (a) shows major features of a trophozoite stage of P. falciparum imaged by transmission EM. The diagram (b) illustrates the mechanism of haemoglobin uptake, digestion and storage in a trophozoite, related in other panels to electron micrographs of (c) the export of adhesive proteins and knobs to the erythrocyte surface via Maurer's clefts, (d) ingestion of haemoglobin through the cytostome, and (e) formation of the malaria pigment haemozoin, which is left uncoloured to show the high density of individual pigment crystals. (f) shows an EM of a schizont during the process of merozoite budding from the main parasite mass (residual body).
Figure 5. (a)–(h) Illustrations of Plasmodium mosquito stages. (a) and (b) show ookinetes of Plasmodium berghei, (a) by light microscopy (Giemsa-stained specimen, left and immuno-fluorescently stained for myosin, right), and (b) by transmission EM showing numerous micronemes, here coloured red, in the anterior region. (c)–(f) show sporozoites of P. berghei expressing green fluorescent protein after transfection, enabling clear visualization by fluorescence microscopy. (c) a female mosquito containing oocysts in its gut wall shows the presence of parasites by green fluorescence in its abdomen (lower arrow) and also some sporozoites in a drop of saliva at the tip of its proboscis (upper arrow); (d)–(f) show the movement of sporozoites gliding in circular trajectories on a glass surface, imaged to trace the direction of gliding, seen in more detail in (e) and (f). The diagram in (g) shows the major structures visible in a Plasmodium sporozoite, with its anterior end towards the right. For comparison, an EM of the anterior part of a P. berghei sporozoite is shown in H, showing the elongated rhoptries and numerous micronemes crowded in this region. Original images shown in (a) were provided by Dr Inga Siden-Kiamos and (b) Dr Anton Dluzewski, Institute of Molecular Biology and Biotechnology, Heraklion, Crete. (c), (d), (e), and (f) were provided by Dr Sylvia Münter and Dr Friedrich Frischknecht, University of Heidelberg Medical School, Heidelberg, Germany. (h) is reproduced by permission of Cambridge University Press from Schrével et al. (2007).
close
 References
    Adams JH, Sim BK, Dolan SA et al. (1992) A family of erythrocyte binding proteins of malaria parasites. Proceedings of the National Academy of Sciences of the USA 89: 7085–7089.
    Aikawa M, Miller LH, Johnson J and Rabbege J (1978) Erythrocyte entry by malarial parasites. A moving junction between erythrocyte and parasite. Journal of Cell Biology 77: 77–82.
    Alano P (2007) Plasmodium falciparum gametocytes: still many secrets of a hidden life. Molecular Microbiology 66: 291–302.
    Amino R, Thiberge S, Martin B et al. (2006) Quantitative imaging of Plasmodium transmission from mosquito to mammal. Nature Medicine 12: 220–224.
    Aurrecoechea C, Brestelli J, Brunk BP et al. (2009) PlasmoDB: a functional genomic database for malaria parasites. Nucleic Acids Research 37: D539–D543.
    Baer K, Klotz C, Kappe SHI, Schnieder T and Frevert U (2007) Release of hepatic Plasmodium yoelii merozoites into the pulmonary microvasculature. PLoS Pathogens 3: e0001–e0018.
    Bannister LH, Hopkins JM, Fowler RE, Krishna S and Mitchell GH (2000) Ultrastructure of rhoptry development in Plasmodium falciparum erythrocytic merozoites. Parasitology 121: 273–287.
    Bannister LH, Hopkins JM, Fowler RE, Krishna S and Mitchell GH (2001) A brief illustrated guide to the ultrastructure of Plasmodium falciparum asexual blood stages. Parastology Today 16: 427–433.
    Bannister LH, Hopkins JM, Margos G, Dluzewski AR and Mitchell GH (2004) Three-dimensional ultrastructure of the ring stage of Plasmodium falciparum: evidence for export pathways. Microscopy and Microanalysis 10: 551–562.
    Baum J, Maier AG, Good RT, Simpson KM and Cowman AF (2005) Invasion by P. falciparum merozoites suggests a hierarchy of molecular interactions. PLoS Pathogens 1: e37.
    Billker O, Lindo V, Panico M et al. (1998) Identification of xanthurenic acid as the putative inducer of malaria development in the mosquito. Nature 392: 289–292.
    Bozdech Z, Llinas M, Pulliam BL et al. (2003) The transcriptome of the intraerythrocytic developmental cycle of Plasmodium falciparum. PLoS Biology 1: e5.
    Cavalier-Smith T (2003) Protist phylogeny and the high-level classification of protozoa. European Journal of Protistology 39: 338–348.
    Chitnis CE and Sharma A (2008) Targeting the Plasmodium vivax Duffy-binding protein. Trends in Parasitology 24: 29–34.
    Cornejo OE and Escalante AA (2006) The origin and age of Plasmodium vivax. Trends in Parasitology 22: 558–563.
    Cowman AF and Crabb BS (2006) Invasion of red blood cells by malaria parasites. Cell 124: 755–766.
    Cox-Singh J and Singh B (2008) Knowlesi malaria: newly emergent and of public health importance? Trends in Parasitology 24: 406–410.
    Cyrklaff M, Kudryashev M, Leis A et al. (2007) Cryoelectron tomography reveals periodic material at the inner side of subpellicular microtubules in apicomplexan parasites. Journal of Experimental Medicine 204: 1281–1287.
    Frevert U (2004) Sneaking in through the back entrance: the biology of malaria liver stages. Trends in Parasitology 20: 417–424.
    Frevert U, Engelmann S, Zougbede S et al. (2005) Intravital observation of Plasmodium berghei sporozoite infection of the liver. PLoS Biology 3: 1034–1046.
    Gardner MJ, Hall N, Fung E et al. (2002) Genome sequence of the human malaria parasite Plasmodium falciparum. Nature 419: 498–511.
    Goldberg DE (2005) Hemoglobin degradation. Current Topics in Microbiology and Immunology 295: 275–291.
    Hall N, Karras M, Raine JD et al. (2005) A comprehensive survey of the Plasmodium life cycle by genomic, transcriptomic, and proteomic analyses. Science 307: 82–86.
    Haynes JD, Diggs CL, Hines FA and Desjardins RE (1976) Culture of human malaria parasites Plasmodium falciparum. Nature 263: 767–769.
    Holder AA (1994) Proteins on the surface of the malaria parasite and cell invasion. Parasitology 108(suppl.): S5–S18.
    Kappe SHI, Kaiser K and Matuschewski K (2003) The Plasmodium sporozoite journey: a rite of passage. Trends in Parasitology 19: 135–143.
    Khan SM (2005) Proteome analysis of separated male and female gametocytes reveals novel sex-specific Plasmodium biology. Cell 121: 675–687.
    Kwiatkowski DP (2005) How malaria has affected the human genome and what human genetics can teach us about malaria. American Journal of Human Genetics 77: 171–192.
    Ladda R, Aikawa M and Sprinz H (1969) Penetration of erythrocytes by merozoites of mammalian and avian malarial parasites. Journal of Parasitology 87: 470–478.
    Lanzer M, Wickert H, Krohne G, Vincensini L and Braun BC (2006) Maurer's clefts: a novel multi-functional organelle in the cytoplasm of Plasmodium falciparum-infected erythrocytes. International Journal for Parasitology 36: 23–36.
    Martinsen ES, Perkins SL and Schall JJ (2008) A three-genome phylogeny of malaria parasites (Plasmodium and closely related genera): evolution of life-history traits and host switches. Molecular Phylogenetics and Evolution 47: 261–273.
    Matuschewski K and Schüler H (2008) Actin/myosin-based gliding motility in apicomplexan parasites. Sub-cellular Biochemistry 47: 110–120.
    Mauritz JMA, Esposito A, Ginsburg H et al. (2009) The homeostasis of Plasmodium falciparum-infected red blood cells. PLoS Computational Biology 5: e1000339.
    Meis JF, Ponnudurai T, Mons B et al. (1990) Plasmodium falciparum: studies on mature exoerythrocytic forms in the liver of the chimpanzee, Pan troglodytes. Experimental Parasitology 70: 1–11.
    Miller LH, Mason SJ, Dvorak JA, McGinniss MH and Rothman IK (1975) Erythrocyte receptors for (Plasmodium knowlesi) malaria: Duffy blood group determinants. Science 189: 561–563.
    Olszewski KL, Morrisey JM, Wilinski D et al. (2009) Host-parasite interactions revealed by Plasmodium falciparum metabolomics. Cell Host and Microbe 5: 191–199.
    Pei X, Guo X, Coppel R et al. (2007) The ring-infected erythrocyte surface antigen (RESA) of Plasmodium falciparum stabilizes spectrin tetramers and suppresses further invasion. Blood 110: 1036–1042.
    Rowe A and Kyes SA (2004) The role of Plasmodium falciparum var genes in malaria in pregnancy. Molecular Microbiology 53: 1011–1019.
    Sauerwein RW (2009) Clinical malaria vaccine development. Immunology Letters 122: 119–121.
    Schrével J, Asfaux-Foucher G, Hopkins JM et al. (2007) Vesicle trafficking during sporozoite development in Plasmodium berghei: ultrastructural evidence for a novel trafficking mechanism. Parasitology 135: 1–12.
    Struck NS, de Souza DS, Langer C et al. (2005) Re-defining the Golgi complex in Plasmodium falciparum using the novel Golgi marker PfGRASP. Journal of Cell Science 118: 5603–5613.
    Sturm A, Graewe S, Franke-Fayard B et al. (2009) Alteration of the parasite plasma membrane and the parasitophorous vacuole membrane during exo-erythrocytic development of malaria parasites. Protist 160: 51–63.
    Trager W and Jensen JB (1976) Human malaria parasites in continuous culture. Science 193: 673–675.
    von Itzstein M, Plebanski M, Cooke BM and Coppel RL (2008) Hot, sweet and sticky: the glycobiology of Plasmodium falciparum. Trends in Parasitology 24: 210–218.
    Walliker D (2005) The hitchhiker's guide to malaria parasite genes. Trends in Parasitology 21: 489–493.
    book WHO (2008) World Malaria Report 2008. Geneva: WHO.
    Yeoh S, O'Donnell RA, Koussis K et al. (2007) Subcellular discharge of a serine protease mediates release of invasive malaria parasites from host erythrocytes. Cell 131: 1072–1083.
    Yu M, Kumar TRS, Nkrumah LJ et al. (2008) The fatty acid biosynthesis enzyme FabI plays a key role in the development of liver-stage malarial parasites. Cell Host and Microbe 4: 567–578.
    Yuda M, Iwanaga S, Shigenobu S et al. (2009) Identification of a transcription factor in the mosquito-invasive stage of malaria parasites. Molecular Microbiology 71: 1402–1414.
 Further Reading
    Carlton JM, Adams JH, Silva JC et al. (2008) Comparative genomics of the neglected human malaria parasite Plasmodium vivax. Nature 455: 757–763.
    Ekland EH and Fidock DA (2007) Advances in understanding the genetic basis of antimalarial drug resistance. Current Opinion in Microbiology 10: 363–370.
    book Garnham PCC (1966) Malaria Parasites and Other Haemosporidia. Oxford: Blackwell.
    Jeffares DC (2007) Genome variation and evolution of the malaria parasite Plasmodium falciparum. Nature Genetics 39: 120–125.
    book Roberts LS and Janovy J (2009) Foundations of Parasitology. New York: McGraw-Hill.
    book Sherman IW (ed.) (2005) Molecular Approaches to Malaria. Washington DC: ASM Press.
    book Sullivan DJ and Krishna S (eds) (2005) Malaria: Drugs, Disease and Post-genomic Biology. Heidelberg: Springer.
    Williams TN (2006) Human red blood cell polymorphisms and malaria. Current Opinion in Microbiology 9: 388–394.
 Websites
    ePath http://malaria.wellcome.ac.uk/
    ePath http://sites.huji.ac.il/malaria/ (H. Ginsburg, Jerusalem)
    ePath http://taxonomicon.taxonomy.nl/
    ePath http://www.dpd.cdc.gov/dpdx/html/imagelibrary/malaria_il.htm
    ePath http://www.plasmodb.org/
    ePath http://www.sanger.ac.uk/Projects/P_falciparum/
    ePath http://www.tulane.edu/~wiser/malaria/cmb.html
    ePath http://www.vivaxmalaria.com/
    ePath http://www.wehi.edu.au/MalDB-www/intro.html
    ePath http://www.who.int/topics/malaria/en/

Related Sub-Topics:

Medical Microbiology | Protozoa
Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

Article Title: Plasmodium
 
How to Cite close
Bannister, Lawrence H, and Sherman, Irwin W(Dec 2009) Plasmodium. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001970.pub2]