Skip to main content

Toxoplasma

  • Chapter
  • First Online:
Molecular Parasitology

Abstract

Toxoplasma gondii is the most widespread intracellular parasite of warm-blooded vertebrates including humans. Infections are mostly asymptomatic or benign in immunocompetent hosts but can be life threatening in immunocompromised individuals and in fetuses after vertical transmission. T. gondii has become a model organism for intracellular parasitism as well as for other Apicomplexa. Genome and transcriptome data for different T. gondii strains are publically available, and powerful forward and reverse genetic tools have been developed. Here we summarize molecular and cellular features of T. gondii that are critical for the biology of the parasite and its interaction with the host. This includes characteristics of the three parasite genomes and how gene expression may be controlled. Examples for T. gondii-specific metabolic features including metabolic pathways of the apicoplast are highlighted. Being an intracellular parasite, the mechanism of host cell invasion is also of major interest. It involves adhesins of the SAG-related sequence protein family, sequential secretion of a large number of proteins from three characteristic secretory organelles (i.e., micronemes, rhoptries, and dense granules), and a unique form of motility accomplished by the “glideosome” multi-protein complex. Polymorphic excretory-secretory proteins from the rhoptries and the dense granules injected into the host cell also extensively modify host responses and determine parasite virulence. Finally, conversion from the proliferative tachyzoite to the dormant bradyzoite stage is critical for the establishment of a chronic infection and allows host (and parasite) survival and transmission to new hosts.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 189.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Azzouz N, Kamena F, Laurino P, Kikkeri R, Mercier C, Cesbron-Delauw MF, Dubremetz JF, De Cola L, Seeberger PH (2013) Toxoplasma gondii secretory proteins bind to sulfated heparin structures. Glycobiology 23:106–120

    Article  CAS  PubMed  Google Scholar 

  • Balaji S, Babu MM, Iyer LM, Aravind L (2005) Discovery of the principal specific transcription factors of Apicomplexa and their implication for the evolution of the AP2-integrase DNA binding domains. Nucleic Acids Res 33:3994–4006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bargieri D, Lagal V, Andenmatten N, Tardieux I, Meissner M, Menard R (2014) Host cell invasion by apicomplexan parasites: the junction conundrum. PLoS Pathog 10, e1004273

    Article  PubMed  PubMed Central  Google Scholar 

  • Baumeister S, Wiesner J, Reichenberg A, Hintz M, Bietz S, Harb OS, Roos DS, Kordes M, Friesen J, Matuschewski K, Lingelbach K, Jomaa H, Seeber F (2011) Fosmidomycin uptake into Plasmodium and Babesia-infected erythrocytes is facilitated by parasite-induced new permeability pathways. PLoS One 6, e19334

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Behnke MS, Radke JB, Smith AT, Sullivan WJ Jr, White MW (2008) The transcription of bradyzoite genes in Toxoplasma gondii is controlled by autonomous promoter elements. Mol Microbiol 68:1502–1518

    Google Scholar 

  • Behnke MS, Wootton JC, Lehmann MM, Radke JB, Lucas O, Nawas J, Sibley LD, White MW (2010) Coordinated progression through two subtranscriptomes underlies the tachyzoite cycle of Toxoplasma gondii. PLoS One 5, e12354

    Article  PubMed  PubMed Central  Google Scholar 

  • Besteiro S, Dubremetz JF, Lebrun M (2011) The moving junction of apicomplexan parasites: a key structure for invasion. Cell Microbiol 13:797–805

    Article  CAS  PubMed  Google Scholar 

  • Botte CY, Dubar F, McFadden GI, Marechal E, Biot C (2012) Plasmodium falciparum apicoplast drugs: targets or off-targets? Chem Rev 112:1269–1283

    Article  CAS  PubMed  Google Scholar 

  • Bougdour A, Maubon D, Baldacci P, Ortet P, Bastien O, Bouillon A, Barale JC, Pelloux H, Menard R, Hakimi MA (2009) Drug inhibition of HDAC3 and epigenetic control of differentiation in Apicomplexa parasites. J Exp Med 206:953–966

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bougdour A, Braun L, Cannella D, Hakimi MA (2010) Chromatin modifications: implications in the regulation of gene expression in Toxoplasma gondii. Cell Microbiol 12:413–423

    Article  CAS  PubMed  Google Scholar 

  • Bougdour A, Tardieux I, Hakimi MA (2014) Toxoplasma exports dense granule proteins beyond the vacuole to the host cell nucleus and rewires the host genome expression. Cell Microbiol 16:334–343

    Article  CAS  PubMed  Google Scholar 

  • Coppens I, Dunn JD, Romano JD, Pypaert M, Zhang H, Boothroyd JC, Joiner KA (2006) Toxoplasma gondii sequesters lysosomes from mammalian hosts in the vacuolar space. Cell 125:261–274

    Google Scholar 

  • Crawford MJ, Thomsen-Zieger N, Ray M, Schachtner J, Roos DS, Seeber F (2006) Toxoplasma gondii scavenges host-derived lipoic acid despite its de novo synthesis in the apicoplast. EMBO J 25:3214–3222

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Crawford J, Lamb E, Wasmuth J, Grujic O, Grigg ME, Boulanger MJ (2010) Structural and functional characterization of SporoSAG: a SAG2-related surface antigen from Toxoplasma gondii. J Biol Chem 285:12063–12070

    Google Scholar 

  • Debierre-Grockiego F, Azzouz N, Schmidt J, Dubremetz JF, Geyer H, Geyer R, Weingart R, Schmidt RR, Schwarz RT (2003) Roles of glycosylphosphatidylinositols of Toxoplasma gondii. Induction of tumor necrosis factor-alpha production in macrophages J Biol Chem 278:32987–32993

    Google Scholar 

  • Dubey JP, Lindsay DS, Speer CA (1998) Structures of Toxoplasma gondii tachyzoites, bradyzoites, and sporozoites and biology and development of tissue cysts. Clin Microbiol Rev 11:267–299

    Google Scholar 

  • Dzierszinski F, Mortuaire M, Cesbron-Delauw MF, Tomavo S (2000) Targeted disruption of the glycosylphosphatidylinositol-anchored surface antigen SAG3 gene in Toxoplasma gondii decreases host cell adhesion and drastically reduces virulence in mice. Mol Microbiol 37:574–582

    Google Scholar 

  • Frenal K, Polonais V, Marq JB, Stratmann R, Limenitakis J, Soldati-Favre D (2010) Functional dissection of the apicomplexan glideosome molecular architecture. Cell Host Microbe 8:343–357

    Article  CAS  PubMed  Google Scholar 

  • Hakimi MA, Deitsch KW (2007) Epigenetics in Apicomplexa: control of gene expression during cell cycle progression, differentiation and antigenic variation. Curr Opin Microbiol 10:357–362

    Article  CAS  PubMed  Google Scholar 

  • He XL, Grigg ME, Boothroyd JC, Garcia KC (2002) Structure of the immunodominant surface antigen from the Toxoplasma gondii SRS superfamily. Nat Struct Biol 9:606–611

    Google Scholar 

  • Hunter CA, Sibley LD (2012) Modulation of innate immunity by Toxoplasma gondii virulence effectors. Nat Rev Microbiol 10:766–778

    Google Scholar 

  • Huynh MH, Carruthers VB (2006) Toxoplasma MIC2 is a major determinant of invasion and virulence. PLoS Pathog 2, e84

    Google Scholar 

  • Huynh MH, Carruthers VB (2007) Microneme protein repertoire and function. In: Ajoika JW, Soldati D (eds) Toxoplasma: molecular and cellular biology, 1st edn. Horizon Bioscience, Norfolk, pp 437–453

    Google Scholar 

  • Jacot D, Meissner M, Sheiner L, Soldati-Favre D, Striepen B (2014) Genetic manipulation of Toxoplasma gondii. In: Weiss LM, Kim K (eds) Toxoplasma gondii: the model apicomplexan-perspective and methods, 2nd edn. Academic, Amsterdam, pp 577–611

    Chapter  Google Scholar 

  • Jacquet A, Coulon L, De Neve J, Daminet V, Haumont M, Garcia L, Bollen A, Jurado M, Biemans R (2001) The surface antigen SAG3 mediates the attachment of Toxoplasma gondii to cell-surface proteoglycans. Mol Biochem Parasitol 116:35–44

    Google Scholar 

  • Jones TC, Hirsch JG (1972) The interaction between Toxoplasma gondii and mammalian cells. II The absence of lysosomal fusion with phagocytic vacuoles containing living parasites J Exp Med 136:1173–1194

    Google Scholar 

  • Khan A, Taylor S, Su C, Sibley L, Paulsen I, Ajioka JW (2007) Genetics and genome organization of Toxoplasma gondii. In: Ajioka J, Soldati D (eds) Toxoplasma: molecular and cellular biology. Horizon Bioscience, Norfolk, pp 193–208

    Google Scholar 

  • Kim SK, Karasov A, Boothroyd JC (2007) Bradyzoite-specific surface antigen SRS9 plays a role in maintaining Toxoplasma gondii persistence in the brain and in host control of parasite replication in the intestine. Infect Immun 75:1626–1634

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kissinger JC, DeBarry J (2011) Genome cartography: charting the apicomplexan genome. Trends Parasitol 27:345–354

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Klotz C, Aebischer T, Seeber F (2012) Stem cell-derived cell cultures and organoids for protozoan parasite propagation and studying host-parasite interaction. Int J Med Microbiol 302:203–209

    Article  CAS  PubMed  Google Scholar 

  • Kohler S, Delwiche CF, Denny PW, Tilney LG, Webster P, Wilson RJ, Palmer JD, Roos DS (1997) A plastid of probable green algal origin in Apicomplexan parasites. Science 275:1485–1489

    Article  CAS  PubMed  Google Scholar 

  • Lebrun M, Carruthers VB, Cesbron-Delauw M-F (2014) Toxoplasma secretory proteins and their roles in cell invasion and intracellular survival. In: Weiss LM, Kim K (eds) Toxoplasma gondii. The model apicomplexan: perspectives and methods, 2nd edn. Elsevier Ltd., Amsterdam/Boston/Heidelberg/London/New York/Oxford/Paris/San Diego/San Francisco/Singapore/Sydney/Tokyo, pp 389–453

    Google Scholar 

  • Lekutis C, Ferguson DJ, Grigg ME, Camps M, Boothroyd JC (2001) Surface antigens of Toxoplasma gondii: variations on a theme. Int J Parasitol 31:1285–1292

    Article  CAS  PubMed  Google Scholar 

  • Lorenzi H, Khan A, Behnke MS, Namasivayam S, Swapna LS, Hadjithomas M, Karamycheva S, Pinney D, Brunk BP, Ajioka JW, Ajzenberg D, Boothroyd JC, Boyle JP, Dardé ML, Diaz-Miranda MA, Dubey JP, Fritz HM, Gennari SM, Gregory BD, Kim K, Saeij JPJ, Su C, White MW, Zhu X-Q, Howe DK, Rosenthal BM, Grigg ME, Parkinson J, Liu L, Kissinger JC, Roos DS, Sibley LD (2016) Local admixture of amplified and diversified secreted pathogenesis determinants shapes mosaic Toxoplasma gondii genomes. Nature Comm 7:10147

    Google Scholar 

  • Mazumdar J, Emma HW, Masek K, Hunter CA, Striepen B (2006) Apicoplast fatty acid synthesis is essential for organelle biogenesis and parasite survival in Toxoplasma gondii. Proc Natl Acad Sci U S A 103:13192–13197

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Minot S, Melo MB, Li F, Lu D, Niedelman W, Levine SS, Saeij JP (2012) Admixture and recombination among Toxoplasma gondii lineages explain global genome diversity. Proc Natl Acad Sci U S A 109:13458–13463

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moore RB, Obornik M, Janouskovec J, Chrudimsky T, Vancova M, Green DH, Wright SW, Davies NW, Bolch CJ, Heimann K, Slapeta J, Hoegh-Guldberg O, Logsdon JM, Carter DA (2008) A photosynthetic alveolate closely related to apicomplexan parasites. Nature 451:959–963

    Article  CAS  PubMed  Google Scholar 

  • Müller IB, Hyde JE (2013) Folate metabolism in human malaria parasites – 75 years on. Mol Biochem Parasitol 188:63–77

    Article  PubMed  Google Scholar 

  • Naguleswaran A, Elias EV, McClintick J, Edenberg HJ, Sullivan WJ Jr (2010) Toxoplasma gondii lysine acetyltransferase GCN5-A functions in the cellular response to alkaline stress and expression of cyst genes. PLoS Pathog 6, e1001232

    Google Scholar 

  • Nair SC, Brooks CF, Goodman CD, Sturm A, McFadden GI, Sundriyal S, Anglin JL, Song Y, Moreno SN, Striepen B (2011) Apicoplast isoprenoid precursor synthesis and the molecular basis of fosmidomycin resistance in Toxoplasma gondii. J Exp Med 208:1547–1559

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Narasimhan J, Joyce BR, Naguleswaran A, Smith AT, Livingston MR, Dixon SE, Coppens I, Wek RC, Sullivan WJ Jr (2008) Translation regulation by eukaryotic initiation factor-2 kinases in the development of latent cysts in Toxoplasma gondii. J Biol Chem 283:16591–16601

    Google Scholar 

  • Olias P, Sibley LD (2016) Functional analysis of Toxoplasma gondii nucleoside triphosphate hydrolases I and II in acute mouse virulence and immune suppression. Infect Immun, IAI.00077-16 [Epub ahead of print]

    Google Scholar 

  • Oppenheim R, Creek D, Macrae J, Modrzynska K, Pino P, Limenitakis J, Polonais V, Seeber F, Barrett M, Billker O, McConville M, Soldati-Favre D (2014) BCKDH: the missing link in apicomplexan mitochondrial metabolism is required for full virulence of Toxoplasma gondii and Plasmodium berghei. PLoS Pathog 10, e1004263

    Article  PubMed  PubMed Central  Google Scholar 

  • Pollard AM, Onatolu KN, Hiller L, Haldar K, Knoll LJ (2008) Highly polymorphic family of glycosylphosphatidylinositol-anchored surface antigens with evidence of developmental regulation in Toxoplasma gondii. Infect Immun 76:103–110

    Google Scholar 

  • Radke JR, Guerini MN, Jerome M, White MW (2003) A change in the premitotic period of the cell cycle is associated with bradyzoite differentiation in Toxoplasma gondii. Mol Biochem Parasitol 131:119–127

    Google Scholar 

  • Radke JR, Donald RG, Eibs A, Jerome ME, Behnke MS, Liberator P, White MW (2006) Changes in the expression of human cell division autoantigen-1 influence Toxoplasma gondii growth and development. PLoS Pathog 2, e105

    Google Scholar 

  • Radke JB, Lucas O, De Silva EK, Ma Y, Sullivan WJ Jr, Weiss LM, Llinas M, White MW (2013) ApiAP2 transcription factor restricts development of the Toxoplasma tissue cyst. Proc Natl Acad Sci U S A 110:6871–6876

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reid AJ, Vermont SJ, Cotton JA, Harris D, Hill-Cawthorne GA, Konen-Waisman S, Latham SM, Mourier T, Norton R, Quail MA, Sanders M, Shanmugam D, Sohal A, Wasmuth JD, Brunk B, Grigg ME, Howard JC, Parkinson J, Roos DS, Trees AJ, Berriman M, Pain A, Wastling JM (2012) Comparative genomics of the apicomplexan parasites Toxoplasma gondii and Neospora caninum: Coccidia differing in host range and transmission strategy. PLoS Pathog 8, e1002567

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Saeij JP, Coller S, Boyle JP, Jerome ME, White MW, Boothroyd JC (2007) Toxoplasma co-opts host gene expression by injection of a polymorphic kinase homologue. Nature 445:324–327

    Google Scholar 

  • Santos JM, Soldati-Favre D (2011) Invasion factors are coupled to key signalling events leading to the establishment of infection in apicomplexan parasites. Cell Microbiol 13:787–796

    Article  CAS  PubMed  Google Scholar 

  • Seeber F, Soldati-Favre D (2010) Metabolic pathways in the apicoplast of apicomplexa. Int Rev Cell Mol Biol 281:161–228

    Article  CAS  PubMed  Google Scholar 

  • Seeber F, Limenitakis J, Soldati-Favre D (2008) Apicomplexan mitochondrial metabolism: a story of gains, losses and retentions. Trends Parasitol 24:468–478

    Article  CAS  PubMed  Google Scholar 

  • Seeber F, Feagin JE, Parsons M (2014) The apicoplast and mitochondrion of Toxoplasma gondii. In: Weiss L, Kim K (eds) Toxoplasma gondii: The model apicomplexan – perspectives and methods, 2nd edn. Academic, Amsterdam, pp 297–350

    Chapter  Google Scholar 

  • Sibley LD, Weidner E, Krahenbuhl JL (1985) Phagosome acidification blocked by intracellular Toxoplasma gondii. Nature 315:416–419

    Google Scholar 

  • Singh U, Brewer JL, Boothroyd JC (2002) Genetic analysis of tachyzoite to bradyzoite differentiation mutants in Toxoplasma gondii reveals a hierarchy of gene induction. Mol Microbiol 44:721–733

    Google Scholar 

  • Su C, Khan A, Zhou P, Majumdar D, Ajzenberg D, Darde ML, Zhu XQ, Ajioka JW, Rosenthal BM, Dubey JP, Sibley LD (2012) Globally diverse Toxoplasma gondii isolates comprise six major clades originating from a small number of distinct ancestral lineages. Proc Natl Acad Sci U S A 109:5844–5849

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sullivan WJ Jr, Narasimhan J, Bhatti MM, Wek RC (2004) Parasite-specific eIF2 (eukaryotic initiation factor-2) kinase required for stress-induced translation control. Biochem J 380:523–531

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Suvorova ES, White MW (2014) Transcript maturation in apicomplexan parasites. Curr Opin Microbiol 20C:82–87

    Article  Google Scholar 

  • Swierzy IJ, Luder CG (2015) Withdrawal of skeletal muscle cells from cell cycle progression triggers differentiation of Toxoplasma gondii towards the bradyzoite stage. Cell Microbiol 17:2–17

    Google Scholar 

  • Tarun A, Vaughan A, Kappe S (2009) Redefining the role of de novo fatty acid synthesis in Plasmodium parasites. Trends Parasitol 25:545–550

    Article  CAS  PubMed  Google Scholar 

  • Taylor S, Barragan A, Su C, Fux B, Fentress SJ, Tang K, Beatty WL, Hajj HE, Jerome M, Behnke MS, White M, Wootton JC, Sibley LD (2006) A secreted serine-threonine kinase determines virulence in the eukaryotic pathogen Toxoplasma gondii. Science 314:1776–1780

    Google Scholar 

  • Tomita T, Bzik DJ, Ma YF, Fox BA, Markillie LM, Taylor RC, Kim K, Weiss LM (2013) The Toxoplasma gondii cyst wall protein CST1 Is critical for cyst wall integrity and promotes bradyzoite persistence. PLoS Pathog 9, e1003823

    Article  PubMed  PubMed Central  Google Scholar 

  • van Dooren GG, Striepen B (2013) The algal past and parasite present of the apicoplast. Annu Rev Microbiol 67:271–289

    Article  PubMed  Google Scholar 

  • Walker R, Gissot M, Croken MM, Huot L, Hot D, Kim K, Tomavo S (2013) The Toxoplasma nuclear factor TgAP2XI-4 controls bradyzoite gene expression and cyst formation. Mol Microbiol 87:641–655

    Article  CAS  PubMed  Google Scholar 

  • Wasmuth JD, Pszenny V, Haile S, Jansen EM, Gast AT, Sher A, Boyle JP, Boulanger MJ, Parkinson J, Grigg ME (2012) Integrated bioinformatic and targeted deletion analyses of the SRS gene superfamily identify SRS29C as a negative regulator of Toxoplasma virulence. MBio 3, e00321-12

    Google Scholar 

  • Wiesner J, Seeber F (2005) The plastid-derived organelle of protozoan human parasites as a target of established and emerging drugs. Expert Opin Ther Targets 9:23–44

    Article  CAS  PubMed  Google Scholar 

Further Reading

  • Ajioka JA, Soldati D (2007) Toxoplasma: Molecular and cellular biology. Horizon, Norfolk

    Google Scholar 

  • Dubey JP (2010) Toxoplasmosis of Animals and Humans, 2nd edn. CRC Press, Boca Raton

    Google Scholar 

  • Francia ME, Striepen B (2014) Cell division in apicomplexan parasites. Nat Rev Microbiol 12:125–136

    Article  CAS  PubMed  Google Scholar 

  • Frenal K, Polonais V, Marq JB, Stratmann R, Limenitakis J, Soldati-Favre D (2010) Functional dissection of the apicomplexan glideosome molecular architecture. Cell Host Microbe 8:343–357

    Article  CAS  PubMed  Google Scholar 

  • Hunter CA, Sibley LD (2012) Modulation of innate immunity by Toxoplasma gondii virulence effectors. Nat Rev Microbiol 10:766–778

    Google Scholar 

  • Montoya JG, Liesenfeld O (2004) Toxoplasmosis. Lancet 363:1965–1976

    Article  CAS  PubMed  Google Scholar 

  • Robert-Gangneux F, Darde ML (2012) Epidemiology of and diagnostic strategies for toxoplasmosis. Clin Microbiol Rev 25:264–296

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Seeber F, Soldati-Favre D (2010) Metabolic pathways in the apicoplast of apicomplexa. Int Rev Cell Mol Biol 281:161–228

    Article  CAS  PubMed  Google Scholar 

  • van Dooren GG, Striepen B (2013) The algal past and parasite present of the apicoplast. Annu Rev Microbiol 67:271–289

    Article  PubMed  Google Scholar 

  • Weiss LM, Kim K (2014) Toxoplasma gondii: the model apicomplexan – perspectives and methods, 2nd edn. Academic, Amsterdam

    Google Scholar 

  • Yarovinsky F (2014) Innate immunity to Toxoplasma gondii infection. Nat Rev Immunol 14:109–121

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Carsten G. K. Lüder .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer-Verlag Wien

About this chapter

Cite this chapter

Lüder, C.G.K., Seeber, F. (2016). Toxoplasma . In: Walochnik, J., Duchêne, M. (eds) Molecular Parasitology. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1416-2_8

Download citation

Publish with us

Policies and ethics