1932

Abstract

Toxoplasmosis is the clinical and pathological consequence of acute infection with the obligate intracellular apicomplexan parasite . Symptoms result from tissue destruction that accompanies lytic parasite growth. This review updates current understanding of the host cell invasion, parasite replication, and eventual egress that constitute the lytic cycle, as well as the ways manipulates host cells to ensure its survival. Since the publication of a previous iteration of this review 15 years ago, important advances have been made in our molecular understanding of parasite growth and mechanisms of host cell egress, and knowledge of the parasite's manipulation of the host has rapidly progressed. Here we cover molecular advances and current conceptual frameworks that include each of these topics, with an eye to what may be known 15 years from now.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-micro-091014-104100
2015-10-15
2024-06-13
Loading full text...

Full text loading...

/deliver/fulltext/micro/69/1/annurev-micro-091014-104100.html?itemId=/content/journals/10.1146/annurev-micro-091014-104100&mimeType=html&fmt=ahah

Literature Cited

  1. Agop-Nersesian C, Egarter S, Langsley G, Foth BJ, Ferguson DJ, Meissner M. 1.  2010. Biogenesis of the inner membrane complex is dependent on vesicular transport by the alveolate specific GTPase Rab11B. PLOS Pathog. 6:e1001029 [Google Scholar]
  2. Agop-Nersesian C, Naissant B, Ben Rached F, Rauch M, Kretzschmar A. 2.  et al. 2009. Rab11A-controlled assembly of the inner membrane complex is required for completion of apicomplexan cytokinesis. PLOS Pathog. 5:e1000270 [Google Scholar]
  3. Alexander DL, Mital J, Ward GE, Bradley P, Boothroyd JC. 3.  2005. Identification of the moving junction complex of Toxoplasma gondii: a collaboration between distinct secretory organelles. PLOS Pathog. 1:e17 [Google Scholar]
  4. Anderson-White BR, Beck JR, Chen CT, Meissner M, Bradley PJ, Gubbels MJ. 4.  2012. Cytoskeleton assembly in Toxoplasma gondii cell division. Int. Rev. Cell Mol. Biol. 298:1–31 [Google Scholar]
  5. Anderson-White BR, Ivey FD, Cheng K, Szatanek T, Lorestani A. 5.  et al. 2011. A family of intermediate filament-like proteins is sequentially assembled into the cytoskeleton of Toxoplasma gondii. Cell Microbiol. 13:18–31 [Google Scholar]
  6. Andrade RM, Wessendarp M, Gubbels MJ, Striepen B, Subauste CS. 6.  2006. CD40 induces macrophage anti-Toxoplasma gondii activity by triggering autophagy-dependent fusion of pathogen-containing vacuoles and lysosomes. J. Clin. Investig. 116:2366–77 [Google Scholar]
  7. Andrade RM, Wessendarp M, Subauste CS. 7.  2003. CD154 activates macrophage antimicrobial activity in the absence of IFN-gamma through a TNF-alpha-dependent mechanism. J. Immunol. 171:6750–56 [Google Scholar]
  8. Arrizabalaga G, Ruiz F, Moreno S, Boothroyd JC. 8.  2004. Ionophore-resistant mutant of Toxoplasma gondii reveals involvement of a sodium/hydrogen exchanger in calcium regulation. J. Cell Biol. 165:653–62 [Google Scholar]
  9. Baum J, Papenfuss AT, Baum B, Speed TP, Cowman AF. 9.  2006. Regulation of apicomplexan actin-based motility. Nat. Rev. Microbiol. 4:621–28 [Google Scholar]
  10. Beck JR, Chen AL, Kim EW, Bradley PJ. 10.  2014. RON5 is critical for organization and function of the Toxoplasma moving junction complex. PLOS Pathog. 10:e1004025 [Google Scholar]
  11. Beck JR, Fung C, Straub KW, Coppens I, Vashisht AA. 11.  et al. 2013. A Toxoplasma palmitoyl acyl transferase and the palmitoylated Armadillo Repeat protein TgARO govern apical rhoptry tethering and reveal a critical role for the rhoptries in host cell invasion but not egress. PLOS Pathog. 9:e1003162 [Google Scholar]
  12. Beck JR, Rodriguez-Fernandez IA, Cruz de Leon J, Huynh MH, Carruthers VB. 12.  et al. 2010. A novel family of Toxoplasma IMC proteins displays a hierarchical organization and functions in coordinating parasite division. PLOS Pathog. 6:e1001094 [Google Scholar]
  13. Behnke MS, Khan A, Wootton JC, Dubey JP, Tang K, Sibley LD. 13.  2011. Virulence differences in Toxoplasma mediated by amplification of a family of polymorphic pseudokinases. PNAS 108:9631–36 [Google Scholar]
  14. Behnke MS, Wootton JC, Lehmann MM, Radke JB, Lucas O. 14.  et al. 2010. Coordinated progression through two subtranscriptomes underlies the tachyzoite cycle of Toxoplasma gondii. PLOS ONE 5:e12354 [Google Scholar]
  15. Besteiro S, Dubremetz JF, Lebrun M. 15.  2011. The moving junction of apicomplexan parasites: A key structure for invasion. Cell. Microbiol. 13:797–805 [Google Scholar]
  16. Bishop JR, Crawford BE, Esko JD. 16.  2005. Cell surface heparan sulfate promotes replication of Toxoplasma gondii. Infect. Immun. 73:5395–401 [Google Scholar]
  17. Black MW, Boothroyd JC. 17.  2000. Lytic cycle of Toxoplasma gondii. Microbiol. Mol. Biol. Rev. 64:607–23 [Google Scholar]
  18. Blader IJ, Manger ID, Boothroyd JC. 18.  2001. Microarray analysis reveals previously unknown changes in Toxoplasma gondii-infected human cells. J. Biol. Chem. 276:24223–31 [Google Scholar]
  19. Bottova I, Sauder U, Olivieri V, Hehl AB, Sonda S. 19.  2010. The P-glycoprotein inhibitor GF120918 modulates Ca2+-dependent processes and lipid metabolism in Toxoplasma gondii. PLOS ONE 5:e10062 [Google Scholar]
  20. Braun L, Brenier-Pinchart MP, Yogavel M, Curt-Varesano A, Curt-Bertini RL. 20.  et al. 2013. A Toxoplasma dense granule protein, GRA24, modulates the early immune response to infection by promoting a direct and sustained host p38 MAPK activation. J. Exp. Med. 210:2071–86 [Google Scholar]
  21. Breinich MS, Ferguson DJ, Foth BJ, van Dooren GG, Lebrun M. 21.  et al. 2009. A dynamin is required for the biogenesis of secretory organelles in Toxoplasma gondii. Curr. Biol. 19:277–86 [Google Scholar]
  22. Brochet M, Collins MO, Smith TK, Thompson E, Sebastian S. 22.  et al. 2014. Phosphoinositide metabolism links cGMP-dependent protein kinase G to essential Ca2+ signals at key decision points in the life cycle of malaria parasites. PLOS Biol. 12:e1001806 [Google Scholar]
  23. Brooks CF, Francia ME, Gissot M, Croken MM, Kim K, Striepen B. 23.  2011. Toxoplasma gondii sequesters centromeres to a specific nuclear region throughout the cell cycle. PNAS 108:3767–72 [Google Scholar]
  24. Brossier F, Jewett TJ, Sibley LD, Urban S. 24.  2005. A spatially localized rhomboid protease cleaves cell surface adhesins essential for invasion by Toxoplasma. PNAS 102:4146–51 [Google Scholar]
  25. Brown KM, Suvorova E, Farrell A, Wiley BB, Marth G. 25.  et al. 2014. Forward genetic screening identifies a small molecule that blocks Toxoplasma gondii growth by inhibiting both host- and parasite-encoded kinases. PLOS Pathog. 10:e1004180 [Google Scholar]
  26. Carmen JC, Sinai AP. 26.  2011. The differential effect of Toxoplasma gondii infection on the stability of BCL2-family members involves multiple activities. Front. Microbiol. 2:1 [Google Scholar]
  27. Carruthers VB, Hakansson S, Giddings OK, Sibley LD. 27.  2000. Toxoplasma gondii uses sulfated proteoglycans for substrate and host cell attachment. Infect. Immun. 68:4005–11 [Google Scholar]
  28. Carruthers VB, Moreno SN, Sibley LD. 28.  1999. Ethanol and acetaldehyde elevate intracellular [Ca2+] and stimulate microneme discharge in Toxoplasma gondii. Biochem. J. 342:Part 2379–86 [Google Scholar]
  29. Carruthers VB, Tomley FM. 29.  2008. Microneme proteins in apicomplexans. Subcell. Biochem. 47:33–45 [Google Scholar]
  30. Cavailles P, Flori P, Papapietro O, Bisanz C, Lagrange D. 30.  et al. 2014. A highly conserved Toxo1 haplotype directs resistance to toxoplasmosis and its associated caspase-1 dependent killing of parasite and host macrophage. PLOS Pathog. 10:e1004005 [Google Scholar]
  31. Cavailles P, Sergent V, Bisanz C, Papapietro O, Colacios C. 31.  et al. 2006. The rat Toxo1 locus directs toxoplasmosis outcome and controls parasite proliferation and spreading by macrophage-dependent mechanisms. PNAS 103:744–49 [Google Scholar]
  32. Chandramohanadas R, Davis PH, Beiting DP, Harbut MB, Darling C. 32.  et al. 2009. Apicomplexan parasites co-opt host calpains to facilitate their escape from infected cells. Science 324:794–97 [Google Scholar]
  33. Chen CT, Gubbels MJ. 33.  2013. The Toxoplasma gondii centrosome is the platform for internal daughter budding as revealed by a Nek1 kinase mutant. J. Cell Sci. 126:3344–55 [Google Scholar]
  34. Chini EN, Nagamune K, Wetzel DM, Sibley LD. 34.  2005. Evidence that the cADPR signalling pathway controls calcium-mediated microneme secretion in Toxoplasma gondii. Biochem. J. 389:269–77 [Google Scholar]
  35. Cirelli KM, Gorfu G, Hassan MA, Printz M, Crown D. 35.  et al. 2014. Inflammasome sensor NLRP1 controls rat macrophage susceptibility to Toxoplasma gondii. PLOS Pathog. 10:e1003927 [Google Scholar]
  36. Collazo CM, Yap GS, Sempowski GD, Lusby KC, Tessarollo L. 36.  et al. 2001. Inactivation of LRG-47 and IRG-47 reveals a family of interferon gamma-inducible genes with essential, pathogen-specific roles in resistance to infection. J. Exp. Med. 194:181–88 [Google Scholar]
  37. Coppens I. 37.  2006. Contribution of host lipids to Toxoplasma pathogenesis. Cell Microbiol. 8:1–9 [Google Scholar]
  38. Coppens I, Dunn JD, Romano JD, Pypaert M, Zhang H. 38.  et al. 2006. Toxoplasma gondii sequesters lysosomes from mammalian hosts in the vacuolar space. Cell 125:261–74 [Google Scholar]
  39. de Leon JC, Scheumann N, Beatty W, Beck JR, Tran JQ. 39.  et al. 2013. A SAS-6-like protein suggests that the Toxoplasma conoid complex evolved from flagellar components. Eukaryot. Cell 12:1009–19 [Google Scholar]
  40. Dobrowolski JM, Niesman IR, Sibley LD. 40.  1997. Actin in the parasite Toxoplasma gondii is encoded by a single copy gene, ACT1 and exists primarily in a globular form. Cell Motil. Cytoskeleton. 37:253–62 [Google Scholar]
  41. Dou Z, McGovern OL, Di Cristina M, Carruthers VB. 41.  2014. Toxoplasma gondii ingests and digests host cytosolic proteins. mBio 5:e01188–14Discovery of an endocytic pathway in Toxoplasma. [Google Scholar]
  42. Dowse TJ, Pascall JC, Brown KD, Soldati D. 42.  2005. Apicomplexan rhomboids have a potential role in microneme protein cleavage during host cell invasion. Int. J. Parasitol. 35:747–56 [Google Scholar]
  43. Dubey JP. 43.  2008. The history of Toxoplasma gondii—the first 100 years. J. Eukaryot. Microbiol. 55:467–75 [Google Scholar]
  44. Egarter S, Andenmatten N, Jackson AJ, Whitelaw JA, Pall G. 44.  et al. 2014. The Toxoplasma Acto-MyoA motor complex is important but not essential for gliding motility and host cell invasion. PLOS ONE 9:e91819 [Google Scholar]
  45. Ewald SE, Chavarria-Smith J, Boothroyd JC. 45.  2014. NLRP1 is an inflammasome sensor for Toxoplasma gondii. Infect. Immun. 82:460–68 [Google Scholar]
  46. Farrell A, Thirugnanam S, Lorestani A, Dvorin JD, Eidell KP. 46.  et al. 2012. A DOC2 protein identified by mutational profiling is essential for apicomplexan parasite exocytosis. Science 335:218–21 [Google Scholar]
  47. Farrell M, Gubbels MJ. 47.  2014. The Toxoplasma gondii kinetochore is required for centrosome association with the centrocone (spindle pole). Cell. Microbiol. 16:78–94 [Google Scholar]
  48. Francia ME, Jordan CN, Patel JD, Sheiner L, Demerly JL. 48.  et al. 2012. Cell division in apicomplexan parasites is organized by a homolog of the striated rootlet fiber of algal flagella. PLOS Biol. 10:e1001444First report on the shared ancesty between endodyogeny and the machinery underlying flagellum construction. [Google Scholar]
  49. Francia ME, Striepen B. 49.  2014. Cell division in apicomplexan parasites. Nat. Rev. Microbiol. 12:125–36 [Google Scholar]
  50. Franco M, Shastri AJ, Boothroyd JC. 50.  2014. Infection by Toxoplasma gondii specifically induces host c-Myc and the genes this pivotal transcription factor regulates. Eukaryot. Cell 13:483–93 [Google Scholar]
  51. Frenal K, Marq JB, Jacot D, Polonais V, Soldati-Favre D. 51.  2014. Plasticity between MyoC- and MyoA-glideosomes: an example of functional compensation in Toxoplasma gondii invasion. PLOS Pathog. 10:e1004504 [Google Scholar]
  52. Frenal K, Polonais V, Marq JB, Stratmann R, Limenitakis J, Soldati-Favre D. 52.  2010. Functional dissection of the apicomplexan glideosome molecular architecture. Cell Host Microbe 8:343–57 [Google Scholar]
  53. Frenal K, Tay CL, Mueller C, Bushell ES, Jia Y. 53.  et al. 2013. Global analysis of apicomplexan protein S-acyl transferases reveals an enzyme essential for invasion. Traffic 14:895–911 [Google Scholar]
  54. Gaji RY, Behnke MS, Lehmann MM, White MW, Carruthers VB. 54.  2011. Cell cycle-dependent, intercellular transmission of Toxoplasma gondii is accompanied by marked changes in parasite gene expression. Mol. Microbiol. 79:192–204 [Google Scholar]
  55. Garrison E, Treeck M, Ehret E, Butz H, Garbuz T. 55.  et al. 2012. A forward genetic screen reveals that calcium-dependent protein kinase 3 regulates egress in Toxoplasma. PLOS Pathog. 8:e1003049 [Google Scholar]
  56. Goebel S, Gross U, Luder CG. 56.  2001. Inhibition of host cell apoptosis by Toxoplasma gondii is accompanied by reduced activation of the caspase cascade and alterations of poly(ADP-ribose) polymerase expression. J. Cell Sci. 114:3495–505 [Google Scholar]
  57. Gorfu G, Cirelli KM, Melo MB, Mayer-Barber K, Crown D. 57.  et al. 2014. Dual role for inflammasome sensors NLRP1 and NLRP3 in murine resistance to Toxoplasma gondii. mBio 5:e01117–13 [Google Scholar]
  58. Gov L, Karimzadeh A, Ueno N, Lodoen MB. 58.  2013. Human innate immunity to Toxoplasma gondii is mediated by host caspase-1 and ASC and parasite GRA15. mBio 4:e00255–13 [Google Scholar]
  59. Gubbels MJ, Duraisingh MT. 59.  2012. Evolution of apicomplexan secretory organelles. Int. J. Parasitol. 42:1071–81 [Google Scholar]
  60. Gubbels MJ, Lehmann M, Muthalagi M, Jerome ME, Brooks CF. 60.  et al. 2008. Forward genetic analysis of the apicomplexan cell division cycle in Toxoplasma gondii. PLOS Pathog. 4:e36 [Google Scholar]
  61. Gubbels MJ, Vaishnava S, Boot N, Dubremetz JF, Striepen B. 61.  2006. A MORN-repeat protein is a dynamic component of the Toxoplasma gondii cell division apparatus. J. Cell Sci. 119:2236–45 [Google Scholar]
  62. Hakansson S, Charron AJ, Sibley LD. 62.  2001. Toxoplasma evacuoles: A two-step process of secretion and fusion forms the parasitophorous vacuole. EMBO J. 20:3132–44 [Google Scholar]
  63. Hakansson S, Morisaki H, Heuser J, Sibley LD. 63.  1999. Time-lapse video microscopy of gliding motility in Toxoplasma gondii reveals a novel, biphasic mechanism of cell locomotion. Mol. Biol. Cell 10:3539–47 [Google Scholar]
  64. Hartmann J, Hu K, He CY, Pelletier L, Roos DS, Warren G. 64.  2006. Golgi and centrosome cycles in Toxoplasma gondii. Mol. Biochem. Parasitol. 145:125–27 [Google Scholar]
  65. He XL, Grigg ME, Boothroyd JC, Garcia KC. 65.  2002. Structure of the immunodominant surface antigen from the Toxoplasma gondii SRS superfamily. Nat. Struct. Biol. 9:606–11 [Google Scholar]
  66. Hoff EF, Carruthers VB. 66.  2002. Is Toxoplasma egress the first step in invasion?. Trends Parasitol. 18:251–55 [Google Scholar]
  67. Hu K. 67.  2008. Organizational changes of the daughter basal complex during the parasite replication of Toxoplasma gondii. PLOS Pathog. 4:e10 [Google Scholar]
  68. Hu K, Johnson J, Florens L, Fraunholz M, Suravajjala S. 68.  et al. 2006. Cytoskeletal components of an invasion machine—the apical complex of Toxoplasma gondii. PLOS Pathog. 2:e13 [Google Scholar]
  69. Hunn JP, Feng CG, Sher A, Howard JC. 69.  2011. The immunity-related GTPases in mammals: a fast-evolving cell-autonomous resistance system against intracellular pathogens. Mamm. Genome 22:43–54 [Google Scholar]
  70. Jensen KD, Hu K, Whitmarsh RJ, Hassan MA, Julien L. 70.  et al. 2013. Toxoplasma gondii rhoptry 16 kinase promotes host resistance to oral infection and intestinal inflammation only in the context of the dense granule protein GRA15. Infect. Immun. 81:2156–67 [Google Scholar]
  71. Johnson TM, Rajfur Z, Jacobson K, Beckers CJ. 71.  2007. Immobilization of the type XIV myosin complex in Toxoplasma gondii. Mol. Biol. Cell 18:3039–46 [Google Scholar]
  72. Jones TC, Hirsch JG. 72.  1972. The interaction between Toxoplasma gondii and mammalian cells. II. The absence of lysosomal fusion with phagocytic vacuoles containing living parasites. J. Exp. Med. 136:1173–94First report showing that host organelles interact with the PV. [Google Scholar]
  73. Kafsack BF, Carruthers VB, Pineda FJ. 73.  2007. Kinetic modeling of Toxoplasma gondii invasion. J. Theor. Biol. 249:817–25 [Google Scholar]
  74. Kafsack BF, Pena JD, Coppens I, Ravindran S, Boothroyd JC, Carruthers VB. 74.  2009. Rapid membrane disruption by a perforin-like protein facilitates parasite exit from host cells. Science 323:530–33 [Google Scholar]
  75. Katris NJ, van Dooren GG, McMillan PJ, Hanssen E, Tilley L, Waller RF. 75.  2014. The apical complex provides a regulated gateway for secretion of invasion factors in Toxoplasma. PLOS Pathog. 10:e1004074 [Google Scholar]
  76. Kessler H, Herm-Gotz A, Hegge S, Rauch M, Soldati-Favre D. 76.  et al. 2008. Microneme protein 8—a new essential invasion factor in Toxoplasma gondii. J. Cell Sci. 121:947–56 [Google Scholar]
  77. Kieschnick H, Wakefield T, Narducci CA, Beckers C. 77.  2001. Toxoplasma gondii attachment to host cells is regulated by a calmodulin-like domain protein kinase. J. Biol. Chem. 276:12369–77 [Google Scholar]
  78. Kim L, Denkers EY. 78.  2006. Toxoplasma gondii triggers Gi-dependent PI 3-kinase signaling required for inhibition of host cell apoptosis. J. Cell Sci. 119:2119–26 [Google Scholar]
  79. Kim SK, Fouts AE, Boothroyd JC. 79.  2007. Toxoplasma gondii dysregulates IFN-gamma-inducible gene expression in human fibroblasts: insights from a genome-wide transcriptional profiling. J. Immunol. 178:5154–65 [Google Scholar]
  80. Kremer K, Kamin D, Rittweger E, Wilkes J, Flammer H. 80.  et al. 2013. An overexpression screen of Toxoplasma gondii Rab-GTPases reveals distinct transport routes to the micronemes. PLOS Pathog. 9:e1003213 [Google Scholar]
  81. Kvaal CA, Radke JR, Guerini MN, White MW. 81.  2002. Isolation of a Toxoplasma gondii cyclin by yeast two-hybrid interactive screen. Mol. Biochem. Parasitol. 120:187–94 [Google Scholar]
  82. Lang C, Hildebrandt A, Brand F, Opitz L, Dihazi H, Luder CG. 82.  2012. Impaired chromatin remodelling at STAT1-regulated promoters leads to global unresponsiveness of Toxoplasma gondii-infected macrophages to IFN-γ. PLOS Pathog. 8:e1002483 [Google Scholar]
  83. Lescault PJ, Thompson AB, Patil V, Lirussi D, Burton A. 83.  et al. 2010. Genomic data reveal Toxoplasma gondii differentiation mutants are also impaired with respect to switching into a novel extracellular tachyzoite state. PLOS ONE 5:e14463 [Google Scholar]
  84. Leung JM, Rould MA, Konradt C, Hunter CA, Ward GE. 84.  2014. Disruption of TgPHIL1 alters specific parameters of Toxoplasma gondii motility measured in a quantitative, three-dimensional live motility assay. PLOS ONE 9:e85763 [Google Scholar]
  85. Li ZH, Ramakrishnan S, Striepen B, Moreno SN. 85.  2013. Toxoplasma gondii relies on both host and parasite isoprenoids and can be rendered sensitive to atorvastatin. PLOS Pathog. 9:e1003665 [Google Scholar]
  86. Lirussi D, Matrajt M. 86.  2011. RNA granules present only in extracellular Toxoplasma gondii increase parasite viability. Int. J. Biol. Sci. 7:960–67 [Google Scholar]
  87. Lorestani A, Sheiner L, Yang K, Robertson SD, Sahoo N. 87.  et al. 2010. A Toxoplasma MORN1 null mutant undergoes repeated divisions but is defective in basal assembly, apicoplast division and cytokinesis. PLOS ONE 5:e12302Demonstrates that the basal complex is the functional ortholog of the contractile ring in cell division. [Google Scholar]
  88. Lourido S, Jeschke GR, Turk BE, Sibley LD. 88.  2013. Exploiting the unique ATP-binding pocket of Toxoplasma calcium-dependent protein kinase 1 to identify its substrates. ACS Chem. Biol. 8:1155–62 [Google Scholar]
  89. Lourido S, Shuman J, Zhang C, Shokat KM, Hui R, Sibley LD. 89.  2010. Calcium-dependent protein kinase 1 is an essential regulator of exocytosis in Toxoplasma. Nature 465:359–62First proof of a Ca2+-dependent protein kinase, a protein family absent from mammals, with an essential role in invasion. [Google Scholar]
  90. Lourido S, Tang K, Sibley LD. 90.  2012. Distinct signalling pathways control Toxoplasma egress and host-cell invasion. EMBO J. 31:4524–34 [Google Scholar]
  91. Lovett JL, Marchesini N, Moreno SN, Sibley LD. 91.  2002. Toxoplasma gondii microneme secretion involves intracellular Ca2+ release from inositol 1,4,5-triphosphate (IP3)/ryanodine-sensitive stores. J. Biol. Chem. 277:25870–76 [Google Scholar]
  92. Luo S, Ruiz FA, Moreno SN. 92.  2005. The acidocalcisome Ca2+-ATPase (TgA1) of Toxoplasma gondii is required for polyphosphate storage, intracellular calcium homeostasis and virulence. Mol. Microbiol. 55:1034–45 [Google Scholar]
  93. Ma JS, Sasai M, Ohshima J, Lee Y, Bando H. 93.  et al. 2014. Selective and strain-specific NFAT4 activation by the Toxoplasma gondii polymorphic dense granule protein GRA6. J. Exp. Med. 211:2013–32 [Google Scholar]
  94. Mann T, Beckers C. 94.  2001. Characterization of the subpellicular network, a filamentous membrane skeletal component in the parasite Toxoplasma gondii. Mol. Biochem. Parasitol. 115:257–68 [Google Scholar]
  95. McCoy JM, Whitehead L, van Dooren GG, Tonkin CJ. 95.  2012. TgCDPK3 regulates calcium-dependent egress of Toxoplasma gondii from host cells. PLOS Pathog. 8:e1003066 [Google Scholar]
  96. Meissner M, Ferguson DJ, Frischknecht F. 96.  2013. Invasion factors of apicomplexan parasites: essential or redundant?. Curr. Opin. Microbiol. 16:438–44 [Google Scholar]
  97. Meissner M, Schluter D, Soldati D. 97.  2002. Role of Toxoplasma gondii myosin A in powering parasite gliding and host cell invasion. Science 298:837–40Shows that myosin A, a class XIVa myosin, is the main motor driving motility and invasion. [Google Scholar]
  98. Melzer T, Duffy A, Weiss LM, Halonen SK. 98.  2008. The gamma interferon (IFN-γ)-inducible GTP-binding protein IGTP is necessary for Toxoplasma vacuolar disruption and induces parasite egression in IFN-γ-stimulated astrocytes. Infect. Immun. 76:4883–94 [Google Scholar]
  99. Mital J, Meissner M, Soldati D, Ward GE. 99.  2005. Conditional expression of Toxoplasma gondii apical membrane antigen-1 (TgAMA1) demonstrates that TgAMA1 plays a critical role in host cell invasion. Mol. Biol. Cell 16:4341–49 [Google Scholar]
  100. Molestina RE, Payne TM, Coppens I, Sinai AP. 100.  2003. Activation of NF-κB by Toxoplasma gondii correlates with increased expression of antiapoptotic genes and localization of phosphorylated IκB to the parasitophorous vacuole membrane. J. Cell Sci. 116:4359–71 [Google Scholar]
  101. Montoya JG, Liesenfeld O. 101.  2004. Toxoplasmosis. Lancet 363:1965–76 [Google Scholar]
  102. Mordue DG, Hakansson S, Niesman I, Sibley LD. 102.  1999. Toxoplasma gondii resides in a vacuole that avoids fusion with host cell endocytic and exocytic vesicular trafficking pathways. Exp. Parasitol. 92:87–99 [Google Scholar]
  103. Morlon-Guyot J, Berry L, Chen CT, Gubbels MJ, Lebrun M, Daher W. 103.  2014. The Toxoplasma gondii calcium dependent protein kinase 7 is involved in early steps of parasite division and is crucial for parasite survival. Cell. Microbiol. 16:95–114 [Google Scholar]
  104. Morrissette NS, Sibley LD. 104.  2002. Disruption of microtubules uncouples budding and nuclear division in Toxoplasma gondii. J. Cell Sci. 115:1017–25 [Google Scholar]
  105. Moudy R, Manning TJ, Beckers CJ. 105.  2001. The loss of cytoplasmic potassium upon host cell breakdown triggers egress of Toxoplasma gondii. J. Biol. Chem. 276:41492–501First comprehensive analysis of the egress mechanism by innovative assays. [Google Scholar]
  106. Muniz-Feliciano L, Van Grol J, Portillo JA, Liew L, Liu B. 106.  et al. 2013. Toxoplasma gondii-induced activation of EGFR prevents autophagy protein-mediated killing of the parasite. PLOS Pathog. 9:e1003809 [Google Scholar]
  107. Nagamune K, Beatty WL, Sibley LD. 107.  2007. Artemisinin induces calcium-dependent protein secretion in the protozoan parasite Toxoplasma gondii. Eukaryot. Cell 6:2147–56 [Google Scholar]
  108. Nagamune K, Hicks LM, Fux B, Brossier F, Chini EN, Sibley LD. 108.  2008. Abscisic acid controls calcium-dependent egress and development in Toxoplasma gondii. Nature 451:207–10 [Google Scholar]
  109. Nagamune K, Moreno SN, Chini EN, Sibley LD. 109.  2008. Calcium regulation and signaling in apicomplexan parasites. Subcell. Biochem. 47:70–81 [Google Scholar]
  110. Nebl T, Prieto JH, Kapp E, Smith BJ, Williams MJ. 110.  et al. 2011. Quantitative in vivo analyses reveal calcium-dependent phosphorylation sites and identifies a novel component of the Toxoplasma invasion motor complex. PLOS Pathog. 7:e1002222 [Google Scholar]
  111. Nishi M, Hu K, Murray JM, Roos DS. 111.  2008. Organellar dynamics during the cell cycle of Toxoplasma gondii. J. Cell Sci. 121:1559–68 [Google Scholar]
  112. Pace DA, McKnight CA, Liu J, Jimenez V, Moreno SN. 112.  2014. Calcium entry in Toxoplasma gondii and its enhancing effect of invasion-linked traits. J. Biol. Chem. 289:19637–47 [Google Scholar]
  113. Payne TM, Molestina RE, Sinai AP. 113.  2003. Inhibition of caspase activation and a requirement for NF-κB function in the Toxoplasma gondii-mediated blockade of host apoptosis. J. Cell Sci. 116:4345–58 [Google Scholar]
  114. Pernas L, Adomako-Ankomah Y, Shastri AJ, Ewald SE, Treeck M. 114.  et al. 2014. Toxoplasma effector MAF1 mediates recruitment of host mitochondria and impacts the host response. PLOS Biol. 12:e1001845 [Google Scholar]
  115. Persson CM, Lambert H, Vutova PP, Dellacasa-Lindberg I, Nederby J. 115.  et al. 2009. Transmission of Toxoplasma gondii from infected dendritic cells to natural killer cells. Infect. Immun. 77:970–76 [Google Scholar]
  116. Persson EK, Agnarson AM, Lambert H, Hitziger N, Yagita H. 116.  et al. 2007. Death receptor ligation or exposure to perforin trigger rapid egress of the intracellular parasite Toxoplasma gondii. J. Immunol. 179:8357–65 [Google Scholar]
  117. Pfefferkorn ER. 117.  1984. Interferon gamma blocks the growth of Toxoplasma gondii in human fibroblasts by inducing the host cells to degrade tryptophan. PNAS 81:908–12 [Google Scholar]
  118. Phelps ED, Sweeney KR, Blader IJ. 118.  2008. Toxoplasma gondii rhoptry discharge correlates with activation of the early growth response 2 host cell transcription factor. Infect. Immun. 76:4703–12 [Google Scholar]
  119. Plattner H, Sehring IM, Mohamed IK, Miranda K, De Souza W. 119.  et al. 2012. Calcium signaling in closely related protozoan groups (Alveolata): non-parasitic ciliates (Paramecium, Tetrahymena) versus parasitic Apicomplexa (Plasmodium, Toxoplasma). Cell Calcium 51:351–82 [Google Scholar]
  120. Pomel S, Luk FC, Beckers CJ. 120.  2008. Host cell egress and invasion induce marked relocations of glycolytic enzymes in Toxoplasma gondii tachyzoites. PLOS Pathog. 4:e1000188 [Google Scholar]
  121. Ramana CV, Gil MP, Schreiber RD, Stark GR. 121.  2002. Stat1-dependent and -independent pathways in IFN-gamma-dependent signaling. Trends Immunol. 23:96–101 [Google Scholar]
  122. Reese ML, Zeiner GM, Saeij JP, Boothroyd JC, Boyle JP. 122.  2011. Polymorphic family of injected pseudokinases is paramount in Toxoplasma virulence. PNAS 108:9625–30 [Google Scholar]
  123. Roiko MS, Svezhova N, Carruthers VB. 123.  2014. Acidification activates Toxoplasma gondii motility and egress by enhancing protein secretion and cytolytic activity. PLOS Pathog. 10:e1004488 [Google Scholar]
  124. Romano JD, Sonda S, Bergbower E, Smith ME, Coppens I. 124.  2013. Toxoplasma gondii salvages sphingolipids from the host Golgi through the rerouting of selected Rab vesicles to the parasitophorous vacuole. Mol. Biol. Cell 24:1974–95 [Google Scholar]
  125. Rosowski EE, Lu D, Julien L, Rodda L, Gaiser RA. 125.  et al. 2011. Strain-specific activation of the NF-κB pathway by GRA15, a novel Toxoplasma gondii dense granule protein. J. Exp. Med. 208:195–212 [Google Scholar]
  126. Rosowski EE, Nguyen QP, Camejo A, Spooner E, Saeij JP. 126.  2014. Toxoplasma gondii inhibits gamma interferon (IFN-γ)- and IFN-β-induced host cell STAT1 transcriptional activity by increasing the association of STAT1 with DNA. Infect. Immun. 82:706–19 [Google Scholar]
  127. Saeij JP, Coller S, Boyle JP, Jerome ME, White MW, Boothroyd JC. 127.  2007. Toxoplasma co-opts host gene expression by injection of a polymorphic kinase homologue. Nature 445:324–27 [Google Scholar]
  128. Sahoo N, Beatty W, Heuser J, Sept D, Sibley LD. 128.  2006. Unusual kinetic and structural properties control rapid assembly and turnover of actin in the parasite Toxoplasma gondii. Mol. Biol. Cell 17:895–906 [Google Scholar]
  129. Sharma P, Chitnis CE. 129.  2013. Key molecular events during host cell invasion by apicomplexan pathogens. Curr. Opin. Microbiol. 16:432–37 [Google Scholar]
  130. Sheffield HG, Melton ML. 130.  1968. The fine structure and reproduction of Toxoplasma gondii. J. Parasitol. 54:209–26 [Google Scholar]
  131. Shen B, Sibley LD. 131.  2014. Toxoplasma aldolase is required for metabolism but dispensable for host-cell invasion. PNAS 111:3567–72 [Google Scholar]
  132. Skillman KM, Diraviyam K, Khan A, Tang K, Sept D, Sibley LD. 132.  2011. Evolutionarily divergent, unstable filamentous actin is essential for gliding motility in apicomplexan parasites. PLOS Pathog. 7:e1002280 [Google Scholar]
  133. Spear W, Chan D, Coppens I, Johnson RS, Giaccia A, Blader IJ. 133.  2006. The host cell transcription factor hypoxia-inducible factor 1 is required for Toxoplasma gondii growth and survival at physiological oxygen levels. Cell Microbiol. 8:339–52 [Google Scholar]
  134. Stommel EW, Ely KH, Schwartzman JD, Kasper LH. 134.  1997. Toxoplasma gondii: Dithiol-induced Ca2+ flux causes egress of parasites from the parasitophorous vacuole. Exp. Parasitol. 87:88–97 [Google Scholar]
  135. Straub KW, Peng ED, Hajagos BE, Tyler JS, Bradley PJ. 135.  2011. The moving junction protein RON8 facilitates firm attachment and host cell invasion in Toxoplasma gondii. PLOS Pathog. 7:e1002007 [Google Scholar]
  136. Striepen B, Jordan CN, Reiff S, van Dooren GG. 136.  2007. Building the perfect parasite: cell division in apicomplexa. PLOS Pathog. 3:e78 [Google Scholar]
  137. Suss-Toby E, Zimmerberg J, Ward GE. 137.  1996. Toxoplasma invasion: The parasitophorous vacuole is formed from host cell plasma membrane and pinches off via a fission pore. PNAS 93:8413–18 [Google Scholar]
  138. Suvorova ES, Francia M, Striepen B, White MW. 138.  2015. A novel bipartite centrosome coordinates the apicomplexan cell cycle. PLOS Biol. 13:e1002093Explains the mechanical basis for how mitosis and daughter budding are coordinated by the centrosome. [Google Scholar]
  139. Suzuki Y, Orellana MA, Schreiber RD, Remington JS. 139.  1988. Interferon-gamma: the major mediator of resistance against Toxoplasma gondii. Science 240:516–18 [Google Scholar]
  140. Tang Q, Andenmatten N, Triana MA, Deng B, Meissner M. 140.  et al. 2014. Calcium-dependent phosphorylation alters Class XIVa myosin function in the protozoan parasite Toxoplasma gondii. Mol. Biol. Cell 25:2579–91 [Google Scholar]
  141. Tomavo S, Slomianny C, Meissner M, Carruthers VB. 141.  2013. Protein trafficking through the endosomal system prepares intracellular parasites for a home invasion. PLOS Pathog. 9:e1003629 [Google Scholar]
  142. Tomita T, Yamada T, Weiss LM, Orlofsky A. 142.  2009. Externally triggered egress is the major fate of Toxoplasma gondii during acute infection. J. Immunol. 183:6667–80 [Google Scholar]
  143. Treeck M, Sanders JL, Elias JE, Boothroyd JC. 143.  2011. The phosphoproteomes of Plasmodium falciparum and Toxoplasma gondii reveal unusual adaptations within and beyond the parasites' boundaries. Cell Host Microbe 10:410–19 [Google Scholar]
  144. Treeck M, Sanders JL, Gaji RY, LaFavers KA, Child MA. 144.  et al. 2014. The calcium-dependent protein kinase 3 of Toxoplasma influences basal calcium levels and functions beyond egress as revealed by quantitative phosphoproteome analysis. PLOS Pathog. 10:e1004197 [Google Scholar]
  145. van Dooren GG, Reiff SB, Tomova C, Meissner M, Humbel BM, Striepen B. 145.  2009. A novel dynamin-related protein has been recruited for apicoplast fission in Toxoplasma gondii. Curr. Biol. 19:267–76 [Google Scholar]
  146. Wetzel DM, Chen LA, Ruiz FA, Moreno SN, Sibley LD. 146.  2004. Calcium-mediated protein secretion potentiates motility in Toxoplasma gondii. J. Cell Sci. 117:5739–48 [Google Scholar]
  147. Wetzel DM, Hakansson S, Hu K, Roos D, Sibley LD. 147.  2003. Actin filament polymerization regulates gliding motility by apicomplexan parasites. Mol. Biol. Cell 14:396–406 [Google Scholar]
  148. Wiley M, Sweeney KR, Chan DA, Brown KM, McMurtrey C. 148.  et al. 2010. Toxoplasma gondii activates hypoxia-inducible factor (HIF) by stabilizing the HIF-1α subunit via type I activin-like receptor kinase receptor signaling. J. Biol. Chem. 285:26852–60 [Google Scholar]
  149. Witola WH, Mui E, Hargrave A, Liu S, Hypolite M. 149.  et al. 2011. NALP1 influences susceptibility to human congenital toxoplasmosis, proinflammatory cytokine response, and fate of Toxoplasma gondii-infected monocytic cells. Infect. Immun. 79:756–66 [Google Scholar]
/content/journals/10.1146/annurev-micro-091014-104100
Loading
/content/journals/10.1146/annurev-micro-091014-104100
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error