is a widespread parasite of warm-blooded vertebrates that also causes opportunistic infections in humans. Rodents are a natural host for asexually replicating forms, whereas cats serve as the definitive host for sexual development. The laboratory mouse provides a model to study pathogenesis. Strains of are globally diverse, with more than 16 distinct haplogroups clustered into 6 major clades. Forward genetic analysis of genetic crosses between different lineages has been used to define the molecular basis of acute virulence in the mouse. These studies have identified a family of secretory serine/threonine rhoptry kinases that target innate immune pathways to protect intracellular parasites from destruction. Rhoptry kinases target immunity-related GTPases, a family of immune effectors that is expanded in rodents. Similar forward genetic studies may be useful to define the basis of pathogenesis in other hosts, including humans, where infections of different strains present with variable clinical severity.


Article metrics loading...

Loading full text...

Full text loading...


Literature Cited

  1. Adams LB, Hibbs JB, Taintor RR, Krahenbuhl JL. 1.  1990. Microbiostatic effect of murine-activated macrophages for Toxoplasma gondii: role for synthesis of inorganic nitrogen oxides from l-arginine. J. Immunol. 144:2725–29 [Google Scholar]
  2. Ajioka JW, Sibley LD. 2.  2013. Development and application of classical genetics in Toxoplasma gondii. Toxoplasma gondii: The Model Apicomplexan—Perspectives and Methods LM Weiss, K Kim 552–76 Amsterdam: Elsevier [Google Scholar]
  3. Ajzenberg D, Cogné N, Paris L, Bessieres MH, Thulliez P. 3.  et al. 2002. Genotype of 86 Toxoplasma gondii isolates associated with human congenital toxoplasmosis and correlation with clinical findings. J. Infect. Dis. 186:684–89 [Google Scholar]
  4. Ajzenberg D, Yera H, Marty P, Paris L, Dalle F. 4.  et al. 2009. Genotype of 88 Toxoplasma gondii isolates associated with toxoplasmosis in immunocompromised patients and correlation with clinical findings. J. Infect. Dis. 199:1155–67 [Google Scholar]
  5. Alaganan A, Fentress SJ, Tang K, Wang Q, Sibley LD. 5.  2013. Toxoplasma GRA7 effector increases turnover of immunity-related GTPases and contributes to acute virulence in the mouse. PNAS 111:1126–31 [Google Scholar]
  6. Behnke MS, Fentress SJ, Mashayekhi M, Li LL, Taylor GA, Sibley LD. 6.  2012. The polymorphic pseudokinase ROP5 controls virulence in Toxoplasma gondii by regulating the active kinase ROP18. PLOS Pathog. 8:e1002992 [Google Scholar]
  7. Behnke MS, Khan A, Lauron EJ, Jimah JR, Wang Q. 7.  et al. 2015. Rhoptry proteins ROP5 and ROP18 are major murine virulence factors in genetically divergent South American strains of Toxoplasma gondii. PLOS Genet 11:e1005434 [Google Scholar]
  8. Behnke MS, Khan A, Sibley LD. 8.  2015. Genetic mapping reveals that sinefungin resistance in Toxoplasma gondii is controlled by a putative amino acid transporter locus that can be used as a negative selectable marker. Eukaryot. Cell 14:140–48 [Google Scholar]
  9. Behnke MS, Khan A, Wootton JC, Dubey JP, Tang K, Sibley LD. 9.  2011. Virulence differences in Toxoplasma mediated by amplification of a family of polymorphic pseudokinases. PNAS 108:9631–36 [Google Scholar]
  10. Beverley JKA. 10.  1959. Congenital transmission of toxoplasmosis through successive generations of mice. Nature 183:1348–49 [Google Scholar]
  11. Boyle JP, Rajasekar B, Saeij JPJ, Ajioka JW, Berriman M. 11.  et al. 2006. Just one cross appears capable of dramatically altering the population biology of a eukaryotic pathogen like Toxoplasma gondii. PNAS 103:10514–19 [Google Scholar]
  12. Carme B, Bissuel F, Ajzenberg D, Bouyne R, Aznar C. 12.  et al. 2002. Severe acquired toxoplasmosis in immunocompetent adult patients in French Guiana. J. Clin. Microbiol. 40:4037–44 [Google Scholar]
  13. Choi J, Park S, Biering SB, Selleck E, Liu CY. 13.  et al. 2014. The parasitophorous vacuole membrane of Toxoplasma gondii is targeted for disruption by ubiquitin-like conjugation systems of autophagy. Immunity 40:924–35 [Google Scholar]
  14. Cong L, Ran FA, Cox D, Lin S, Barretto R. 14.  et al. 2013. Multiplex genome engineering using CRISPR/Cas systems. Science 339:819–23 [Google Scholar]
  15. Cornelissen AWCA, Overdulve JP. 15.  1985. Sex determination and sex differentiation in coccidia: gametogony and oocyst production after monoclonal infection of cats with free-living and intermediate host stages of Isospora (Toxoplasma) gondii. Parasitology 90:35–44 [Google Scholar]
  16. Cornelissen AWCA, Overdulve JP, Van der Ploeg M. 16.  1984. Determination of nuclear DNA of five eucoccidian parasites, Isospora (Toxoplasma) gondii, Sarcocystis cruzi, Eimeria tenella, E. acervulina, and Plasmodium berghei, with special reference to gametogenesis and meiosis in I. (T.) gondii. Parasitology 88:531–53 [Google Scholar]
  17. Dardé ML, Bouteille B, Pestre-Alexandre M. 17.  1992. Isoenzyme analysis of 35 Toxoplasma gondii isolates and the biological and epidemiological implications. J. Parasitol. 78:786–94 [Google Scholar]
  18. Degrandi D, Kravets E, Konermann C, Beuter-Gunia C, Klumpers V. 18.  et al. 2013. Murine guanylate binding protein 2 (mGBP2) controls Toxoplasma gondii replication. PNAS 110:294–99 [Google Scholar]
  19. Demar M, Hommel D, Djossou F, Peneau C, Boukhari R. 19.  et al. 2012. Acute toxoplasmoses in immunocompetent patients hospitalized in an intensive care unit in French Guiana. Clin. Microbiol. Infect. 18:E221–31 [Google Scholar]
  20. Deretic V, Saitoh T, Akira S. 20.  2013. Autophagy in infection, inflammation and immunity. Nat. Rev. Immunol. 13:722–37 [Google Scholar]
  21. Dubey JP. 21.  1977. Toxoplasma, Hammondia, Besniotia, Sarcocystis, and other tissue cyst-forming coccidia of man and animals. Parasitic Protozoa JP Kreier 101–237 New York: Academic Press [Google Scholar]
  22. Dubey JP. 22.  1997. Bradyzoite-induced murine toxoplasmosis: Stage conversion pathogenesis, and tissue cyst formation in mice fed bradyzoites of different strains of Toxoplasma gondii. J. Eukaryot. Microbiol. 44:592–602 [Google Scholar]
  23. Dubey JP. 23.  2008. Toxoplasma gondii infections in chickens (Gallus domesticus): prevalence, clinical disease, diagnosis, and public health significance. Zoonoses Public Health 57:60–73 [Google Scholar]
  24. Dubey JP. 24.  2010. Toxoplasmosis of Animals and Humans Boca Raton, FL: CRC [Google Scholar]
  25. Dubey JP, Ferreira LR, Martins J, McLeod R. 25.  2012. Oral oocyst-induced mouse model of toxoplasmosis: effect of infection with Toxoplasma gondii strains of different genotypes, dose, and mouse strains (transgenic, out-bred, in-bred) on pathogenesis and mortality. Parasitology 139:1–13 [Google Scholar]
  26. Dubey JP, Frenkel JK. 26.  1998. Toxoplasmosis of rats: a review, with considerations of their value as an animal model and their possible role in epidemiology. Vet. Parasitol. 77:1–32 [Google Scholar]
  27. Dubey JP, Kirkbride CA. 27.  1984. Epizootics of ovine abortion due to Toxoplasma gondii in north central United States. J. Am. Vet. Medical Assoc. 184:657–60 [Google Scholar]
  28. Dubey JP, Shen SK, Kwok OCH, Thulliez P. 28.  1997. Toxoplasmosis in rats (Rattus norvegicus): congenital transmission to first and second generation offspring and isolation of Toxoplasma gondii from seronegative rats. Parasitology 115:9–14 [Google Scholar]
  29. Dubey JP, Van Why K, Verma SK, Choudhary S, Kwok OC. 29.  et al. 2014. Genotyping Toxoplasma gondii from wildlife in Pennsylvania and identification of natural recombinants virulent to mice. Vet. Parasitol. 200:74–84 [Google Scholar]
  30. Dubey JP, Velmurugan GV, Rajendran C, Yabsley MJ, Thomas NJ. 30.  et al. 2011. Genetic characterisation of Toxoplasma gondii in wildlife from North America revealed widespread and high prevalence of the fourth clonal type. Int. J. Parasitol. 41:1139–47 [Google Scholar]
  31. Dubey JP, Zhu XQ, Sundar N, Zhang H, Kwok OC, Su C. 31.  2007. Genetic and biologic characterization of Toxoplasma gondii isolates of cats from China. Vet. Parasitol. 145:352–56 [Google Scholar]
  32. Dupont CD, Christian DA, Hunter CA. 32.  2012. Immune response and immunopathology during toxoplasmosis. Semin. Immunopathol. 34:793–813 [Google Scholar]
  33. Etheridge RD, Alagan A, Tang K, Turk BE, Sibley LD. 33.  2014. ROP18 and ROP17 kinase complexes synergize to control acute virulence of Toxoplasma in the mouse. Cell Host Microbe 15:537–50 [Google Scholar]
  34. Fentress SJ, Behnke MS, Dunay IR, Moashayekhi M, Rommereim LM. 34.  et al. 2010. Phosphorylation of immunity-related GTPases by a parasite secretory kinase promotes macrophage survival and virulence. Cell Host Microbe 16:484–95 [Google Scholar]
  35. Fentress SJ, Sibley LD. 35.  2011. The secreted kinase ROP18 defends Toxoplasma's border. Bioessays 33:693–700 [Google Scholar]
  36. Fleckenstein MC, Reese ML, Könen-Waisman S, Boothroyd JC, Howard JC, Steinfeldt T. 36.  2012. A Toxoplasma gondii pseudokinase inhibits host IRG resistance proteins. PLOS Biol. 10:e1001358 [Google Scholar]
  37. Frenkel JK. 37.  1953. Host, strain and treatment variation as factors in the pathogenesis of toxoplasmosis. Am. J. Trop. Med. Hyg. 2:390–415 [Google Scholar]
  38. Frenkel JK, Dubey JP, Miller NL. 38.  1970. Toxoplasma gondii in cats: fecal stages identified as coccidian oocysts. Science 167:893–96 [Google Scholar]
  39. Fux B, Nawas J, Khan A, Gill DB, Su C, Sibley LD. 39.  2007. Toxoplasma gondii strains defective in oral transmission are also defective in developmental stage differentiation. Infect. Immun. 75:2580–90 [Google Scholar]
  40. Gazzinelli RT, Mendonca-Neto R, Lilue J, Howard J, Sher A. 40.  2014. Innate resistance against Toxoplasma gondii: an evolutionary tale of mice, cats, and men. Cell Host Microbe 15:132–38 [Google Scholar]
  41. Ghosh A, Uthaiah R, Howard J, Herrmann C, Wolf E. 41.  2004. Crystal structure of IIGP1: a paradigm for interferon-inducible p47 resistance GTPases. Mol. Cell 15:727–39 [Google Scholar]
  42. Håkansson S, Charron AJ, Sibley LD. 42.  2001. Toxoplasma evacuoles: A two-step process of secretion and fusion forms the parasitophorous vacuole. Embo J. 20:3132–44 [Google Scholar]
  43. Hermanns T, Müller UB, Könen-Waisman S, Howard JC, Steinfeldt T. 43.  2016. The Toxoplasma gondii rhoptry protein ROP18 is an Irga6-specific kinase and regulated by the dense granule protein GRA7. Cell Microbiol. 18:244–59 [Google Scholar]
  44. Howard JC, Hunn JP, Steinfeldt T. 44.  2011. The IRG protein-based resistance mechanism in mice and its relation to virulence in Toxoplasma gondii. Curr. Opin. Microbiol. 14:414–21 [Google Scholar]
  45. Howe DK, Honoré S, Derouin F, Sibley LD. 45.  1997. Determination of genotypes of Toxoplasma gondii strains isolated from patients with toxoplasmosis. J. Clin. Microbiol. 35:1411–14 [Google Scholar]
  46. Howe DK, Sibley LD. 46.  1995. Toxoplasma gondii comprises three clonal lineages: correlation of parasite genotype with human disease. J. Infect. Dis. 172:1561–66 [Google Scholar]
  47. Howe DK, Summers BC, Sibley LD. 47.  1996. Acute virulence in mice is associated with markers on chromosome VIII in Toxoplasma gondii. Infect. Immun. 64:5193–98 [Google Scholar]
  48. Huang J, Brumell JH. 48.  2014. Bacteria-autophagy interplay: a battle for survival. Nat. Rev. Microbiol. 12:101–14 [Google Scholar]
  49. Hunter CA, Sibley LD. 49.  2012. Modulation of innate immunity by Toxoplasma gondii virulence effectors. Nat. Rev. Microbiol. 10:766–78 [Google Scholar]
  50. Israelski DM, Remington JS. 50.  1993. Toxoplasmosis in the non-AIDS immunocompromised host. Curr. Clin. Top. Infect. Dis. 13:322–56 [Google Scholar]
  51. Jones JL, Dubey JP. 51.  2010. Waterborne toxoplasmosis—recent developments. Exp. Parasitol. 124:10–25 [Google Scholar]
  52. Jones JL, Dubey JP. 52.  2012. Foodborne toxoplasmosis. Clin. Infect. Dis. 55:845–51 [Google Scholar]
  53. Jones JL, Kruszon-Moran D, Wilson M, McQuillan G, Navin T, McAuley JB. 53.  2001. Toxoplasma gondii infection in the United States: seroprevalence and risk factors. Am. J. Epidemiol. 154:357–65 [Google Scholar]
  54. Khaminets A, Hunn JP, Könen-Waisman S, Zhao YO, Preukschat D. 54.  et al. 2010. Coordinated loading of IRG resistance GTPases on to the Toxoplasma gondii parasitophorous vacuole. Cell Microbiol. 12:939–61 [Google Scholar]
  55. Khan A, Ajzenberg D, Mercier A, Demar M, Simon S. 55.  et al. 2014. Geographic separation of domestic and wild strains of Toxoplasma gondii in French Guiana correlates with a monomorphic version of chromosome 1a. PLOS Negl. Trop. Dis. 8:e3182 [Google Scholar]
  56. Khan A, Bohme U, Kelly KA, Adlem E, Brooks K. 56.  et al. 2006. Common inheritance of chromosome Ia associated with clonal expansion of Toxoplasma gondii. Gen. Res. 16:1119–25 [Google Scholar]
  57. Khan A, Dubey JP, Su C, Ajioka JW, Rosenthal BM, Sibley LD. 57.  2011. Genetic analyses of atypical Toxoplasma gondii strains reveal a fourth clonal lineage in North America. Int. J. Parasitol. 41:645–55 [Google Scholar]
  58. Khan A, Fux B, Su C, Dubey JP, Darde ML. 58.  et al. 2007. Recent transcontinental sweep of Toxoplasma gondii driven by a single monomorphic chromosome. PNAS 104:14872–77 [Google Scholar]
  59. Khan A, Jordan C, Muccioli C, Vallochi AL, Rizzo LV. 59.  et al. 2006. Genetic divergence of Toxoplasma gondii strains associated with ocular toxoplasmosis Brazil. Emerg. Infect. Dis. 12:942–49 [Google Scholar]
  60. Khan A, Shaik JS, Behnke M, Wang Q, Dubey JP. 60.  et al. 2014. NextGen sequencing reveals short double crossovers contribute disproportionately to genetic diversity in Toxoplasma gondii. BMC Genomics 15:1168 [Google Scholar]
  61. Khan A, Su C, German M, Storch GA, Clifford D, Sibley LD. 61.  2005. Genotyping of Toxoplasma gondii strains from immunocompromised patients reveals high prevalence of type I strains. J. Clin. Microbiol. 43:5881–87 [Google Scholar]
  62. Khan A, Taylor S, Ajioka JW, Rosenthal BM, Sibley LD. 62.  2009. Selection at a single locus leads to widespread expansion of Toxoplasma gondii lineages that are virulent in mice. PLOS Genet. 5:e1000404 [Google Scholar]
  63. Khan A, Taylor S, Su C, Mackey AJ, Boyle J. 63.  et al. 2005. Composite genome map and recombination parameters derived from three archetypal lineages of Toxoplasma gondii. Nucleic Acids Res. 33:2980–92 [Google Scholar]
  64. Lander E, Kruglyak L. 64.  1995. Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nat. Genet. 11:241–47 [Google Scholar]
  65. Lander ES, Botstein D. 65.  1989. Mapping mendelian factors underlying quantitative traits using RFLP linkage maps. Genetics 121:185–99 [Google Scholar]
  66. Lang C, Griss U, Luder CGK. 66.  2007. Subversion of innate and adaptive immune responses by Toxoplasma gondii. Parasitol. Res. 100:191–203 [Google Scholar]
  67. Lehmann T, Marcet PL, Graham DH, Dahl ER, Dubey JP. 67.  2006. Globalization and the population structure of Toxoplasma gondii. PNAS 103:11423–28 [Google Scholar]
  68. Levine B, Mizushima N, Virgin HW. 68.  2011. Autophagy in immunity and inflammation. Nature 469:323–35 [Google Scholar]
  69. Liesenfeld O. 69.  2002. Oral infection of C57BL/6 mice with Toxoplasma gondii: a new model of inflammatory bowel disease?. J. Infect. Dis. 185:S96–101 [Google Scholar]
  70. Lilue J, Müller UB, Steinfeldt T, Howard JC. 70.  2013. Reciprocal virulence and resistance polymorphism in the relationship between Toxoplasma gondii and the house mouse. eLife 2:e01298 [Google Scholar]
  71. Long S, Wang Q, Sibley LD. 71.  2016. Analysis of noncanonical calcium-dependent protein kinases in Toxoplasma gondii by targeted gene deletion using CRISPR/Cas9. Infect. Immun. 841262–73 [Google Scholar]
  72. Lorenzi H, Khan A, Behnke MS, Namasivayam S, Swapna LS. 72.  et al. 2016. Local admixture of amplified and diversified secreted pathogenesis determinants shapes mosaic Toxoplasma gondii genomes. Nat. Commun. 7:10147 [Google Scholar]
  73. Luft BJ, Remington JS. 73.  1992. Toxoplasmic encephalitis in AIDS. Clin. Infect. Dis. 15:211–22 [Google Scholar]
  74. MacMicking JD. 74.  2012. Interferon-inducible effector mechanisms in cell-autonomous immunity. Nat. Rev. Immunol. 12:367–82 [Google Scholar]
  75. Mali P, Esvelt KM, Church GM. 75.  2013. Cas9 as a versatile tool for engineering biology. Nat. Methods 10:957–63 [Google Scholar]
  76. McCabe RE. 76.  2001. Antitoxoplasma chemotherapy. Toxoplasmosis: A Comprehensive Clinical Guide DHM Joynson, TG Wreghitt 319–59 Cambridge, UK: Cambridge Univ. Press [Google Scholar]
  77. Mercier A, Ajzenberg D, Devillard S, Demar MP, de Thoisy B. 77.  et al. 2011. Human impact on genetic diversity of Toxoplasma gondii: example of the anthropized environment from French Guiana. Infect. Genet. Evol. 11:1378–87 [Google Scholar]
  78. Mercier A, Devillard S, Ngoubangoye B, Bonnabau H, Banuls AL. 78.  et al. 2010. Additional haplogroups of Toxoplasma gondii out of Africa: population structure and mouse-virulence of strains from Gabon. PLOS Negl. Trop. Dis. 4:e876 [Google Scholar]
  79. Miller NL, Frenkel JK, Dubey JP. 79.  1972. Oral infections with Toxoplasma cysts and oocysts in felines, other mammals, and in birds. J. Parasitol. 58:928–37 [Google Scholar]
  80. Montoya JG, Liesenfeld O. 80.  2004. Toxoplasmosis. Lancet 363:1965–76 [Google Scholar]
  81. Nathan C, Shiloh MU. 81.  2000. Reactive oxygen and nitrogen intermediates in the relationship between mammalian hosts and microbial pathogens. PNAS 97:8841–48 [Google Scholar]
  82. Niedelman W, Gold DA, Rosowski EE, Sprokholt JK, Lim D. 82.  et al. 2012. The rhoptry proteins ROP18 and ROP5 mediate Toxoplasma gondii evasion of the murine, but not the human, interferon-gamma response. PLOS Pathog. 8:e1002784 [Google Scholar]
  83. Ohshima J, Lee Y, Sasai M, Saitoh T, Su Ma J. 83.  et al. 2014. Role of mouse and human autophagy proteins in IFN-gamma-induced cell-autonomous responses against Toxoplasma gondii. J. Immunol. 192:3328–35 [Google Scholar]
  84. Ong YC, Reese ML, Boothroyd JC. 84.  2010. Toxoplasma rhoptry protein 16 (ROP16) subverts host function by direct tyrosine phosphorylation of STAT6. J. Biol. Chem. 285:28731–40 [Google Scholar]
  85. Pappas G, Roussos N, Falagas ME. 85.  2009. Toxoplasmosis snapshots: global status of Toxoplasma gondii seroprevalence and implications for pregnancy and congenital toxoplasmosis. Int. J. Parasitol. 39:1385–94 [Google Scholar]
  86. Pawlowski J, Audic S, Adl S, Bass D, Belbahri L. 86.  et al. 2012. CBOL protist working group: barcoding eukaryotic richness beyond the animal, plant, and fungal kingdoms. PLOS Biol. 10:e1001419 [Google Scholar]
  87. Pawlowski N, Khaminets A, Hunn JP, Papic N, Schmidt A. 87.  et al. 2011. The activation mechanism of Irga6, an interferon-inducible GTPase contributing to mouse resistance against Toxoplasma gondii. BMC Biol. 9:7 [Google Scholar]
  88. Peixoto L, Chen F, Harb OS, Davis PH, Beiting DP. 88.  et al. 2010. Integrative genomics approaches highlight a family of parasite-specific kinases that regulate host responses. Cell Host Microbe 8:208–18 [Google Scholar]
  89. Pfaff AW, Liesenfeld O, Candolfi E. 89.  2007. Congenital toxoplasmosis. Toxoplasma: Molecular and Cellular Biology JW Ajioka, D Soldati 93–110 Norfolk, UK: Horizon Biosci. [Google Scholar]
  90. Pfefferkorn ER. 90.  1984. Interferon-gamma blocks the growth of Toxoplasma gondii in human fibroblasts by inducing the host to degrade tryptophan. PNAS 81:908–12 [Google Scholar]
  91. Pfefferkorn ER, Kasper LH. 91.  1983. Toxoplasma gondii: Genetic crosses reveal phenotypic suppression of hydroxyurea resistance by fluorodeoxyuridine resistance. Exp. Parasitol. 55:207–18 [Google Scholar]
  92. Pfefferkorn ER, Pfefferkorn LC. 92.  1977. Toxoplasma gondii: characterization of a mutant resistant to 5-fluorodeoxyuridine. Exp. Parasitol. 42:44–55 [Google Scholar]
  93. Pfefferkorn ER, Pfefferkorn LC. 93.  1979. Quantitative studies of the mutagenesis of Toxoplasma gondii. J. Parasitol. 65:363–70 [Google Scholar]
  94. Pfefferkorn ER, Pfefferkorn LC, Colby ED. 94.  1977. Development of gametes and oocysts in cats fed cysts derived from cloned trophozoites of Toxoplasma gondii. J. Parasitol. 63:158–59 [Google Scholar]
  95. Pfefferkorn LC, Pfefferkorn ER. 95.  1980. Toxoplasma gondii: genetic recombination between drug resistant mutants. Exp. Parasitol. 50:305–16 [Google Scholar]
  96. Reese ML, Boothroyd JC. 96.  2011. A conserved non-canonical motif in the pseudoactive site of the ROP5 pseudokinase domain mediates its effect on Toxoplasma virulence. J. Biol. Chem. 286:29366–75 [Google Scholar]
  97. Reese ML, Shah N, Boothroyd JC. 97.  2014. The Toxoplasma pseudokinase ROP5 is an allosteric inhibitor of the immunity-related GTPases. J. Biol. Chem. 289:27849–58 [Google Scholar]
  98. Reese ML, Zeiner GM, Saeij JP, Boothroyd JC, Boyle JP. 98.  2011. Polymorphic family of injected pseudokinases is paramount in Toxoplasma virulence. PNAS 108:9625–30 [Google Scholar]
  99. Roos DS, Donald RGK, Morrissette NS, Moulton AL. 99.  1994. Molecular tools for genetic dissection of the protozoan parasite Toxoplasma gondii. Methods Cell Biol. 45:28–61 [Google Scholar]
  100. Rosowski EE, Lu D, Julien L, Rodda L, Gaiser RA. 100.  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]
  101. Saeij JPJ, Boyle JP, Coller S, Taylor S, Sibley LD. 101.  et al. 2006. Polymorphic secreted kinases are key virulence factors in toxoplasmosis. Science 314:1780–83 [Google Scholar]
  102. Saeij JPJ, Coller S, Boyle JP, Jerome ME, White ME, Boothroyd JC. 102.  2007. Toxoplasma co-opts host gene expression by injection of a polymorphic kinase homologue. Nature 445:324–27 [Google Scholar]
  103. Schreiner M, Liesenfeld O. 103.  2009. Small intestinal inflammation following oral infection with Toxoplasma gondii does not occur exclusively in C57BL/6 mice: review of 70 reports from the literature. Mem. Inst. Oswaldo Cruz 104:221–33 [Google Scholar]
  104. Selleck EM, Fentress SJ, Beatty WL, Degrandi D, Pfeffer K. 104.  et al. 2013. Guanylate-binding protein 1 (Gbp1) contributes to cell-autonomous immunity against Toxoplasma gondii. PLOS Pathog. 9:e1003320 [Google Scholar]
  105. Selleck EM, Orchard RC, Lassen KG, Beatty WL, Xavier RJ. 105.  et al. 2015. A noncanonical autophagy pathway restricts Toxoplasma gondii growth in a strain-specific manner in IFN-gamma-activated human cells. mBio 6:e01157–15 [Google Scholar]
  106. Shaik J, Khan A, Beverley SM, Sibley LD. 106.  2015. REDHORSE-REcombination and Double crossover detection in Haploid Organisms using next geneRation SEquencing data. BMC Genomics 16:133 [Google Scholar]
  107. Shen B, Brown KM, Lee TD, Sibley LD. 107.  2014. Efficient gene disruption in diverse strains of Toxoplasma gondii using CRISPR/CAS9. mBio 5:3e01114–14 [Google Scholar]
  108. Sibley LD, Ajioka JW. 108.  2008. Population structure of Toxoplasma gondii: clonal expansion driven by infrequent recombination and selective sweeps. Annu. Rev. Microbiol. 62:329–51 [Google Scholar]
  109. Sibley LD, Boothroyd JC. 109.  1992. Construction of a molecular karyotype for Toxoplasma gondii. Mol. Biochem. Parasitol. 51:291–300 [Google Scholar]
  110. Sibley LD, Boothroyd JC. 110.  1992. Virulent strains of Toxoplasma gondii comprise a single clonal lineage. Nature 359:82–85 [Google Scholar]
  111. Sibley LD, LeBlanc AJ, Pfefferkorn ER, Boothroyd JC. 111.  1992. Generation of a restriction fragment length polymorphism linkage map for Toxoplasma gondii. Genetics 132:1003–15 [Google Scholar]
  112. Sidik SM, Hackett CG, Tran F, Westwood NJ, Lourido S. 112.  2014. Efficient genome engineering of Toxoplasma gondii using CRISPR/Cas9. PLOS ONE 9:e100450 [Google Scholar]
  113. Steinfeldt T, Könen-Waisman S, Tong L, Pawlowski N, Lamkemeyer T. 113.  et al. 2010. Phosphorylation of mouse immunity-related GTPase (IRG) resistance proteins is an evasion strategy for virulent Toxoplasma gondii. PLOS Biol. 8:e1000576 [Google Scholar]
  114. Su C, Evans D, Cole RH, Kissinger JC, Ajioka JW, Sibley LD. 114.  2003. Recent expansion of Toxoplasma through enhanced oral transmission. Science 299:414–16 [Google Scholar]
  115. Su C, Howe DK, Dubey JP, Ajioka JW, Sibley LD. 115.  2002. Identification of quantitative trait loci controlling acute virulence in Toxoplasma gondii. PNAS 99:10753–58 [Google Scholar]
  116. Su CL, Khan A, Zhou P, Majumdar D, Ajzenberg D. 116.  et al. 2012. Globally diverse Toxoplasma gondii isolates comprise six major clades originating from a small number of distinct ancestral lineages. PNAS 109:5844–49 [Google Scholar]
  117. Subauste CS. 117.  2009. Autophagy in immunity against Toxoplasma gondii. Curr. Top. Microbiol. Immunol. 335:251–65 [Google Scholar]
  118. Suzuki Y, Conley FK, Remington JS. 118.  1989. Differences in virulence and development of encephalitis during chronic infection vary with the strain of Toxoplasma gondii. J. Infect. Dis. 159:790–94 [Google Scholar]
  119. Suzuki Y, Joh K. 119.  1994. Effect of the strain of Toxoplasma gondii on the development of toxoplasmic encephalitis in mice treated with antibody to interferon-gamma. Parasitol. Res. 80:125–30 [Google Scholar]
  120. Suzuki Y, Yang Q, Remington JS. 120.  1995. Genetic resistance against acute toxoplasmosis depends on the strain of Toxoplasma gondii. J. Parasitol. 81:1032–34 [Google Scholar]
  121. Taylor GA, Feng CG, Sher A. 121.  2007. Control of IFN-gamma-mediated host resistance to intracellular pathogens by immunity-related GTPases (p47 GTPases). Microb. Infect. 9:1644–51 [Google Scholar]
  122. Taylor S, Barragan A, Su C, Fux B, Fentress SJ. 122.  et al. 2006. A secreted serine-threonine kinase determines virulence in the eukaryotic pathogen Toxoplasma gondii. Science 314:1776–80 [Google Scholar]
  123. Traver MK, Henry SC, Cantillana V, Oliver T, Hunn JP. 123.  et al. 2011. Immunity-related GTPase M (IRGM) proteins influence the localization of guanylate-binding protein 2 (GBP2) by modulating macroautophagy. J. Biol. Chem. 286:30471–80 [Google Scholar]
  124. Wilson CB, Tsai V, Remington JS. 124.  1980. Failure to trigger the oxidative burst of normal macrophages. J. Exp. Med. 151:328–46 [Google Scholar]
  125. Yamamoto M, Ma JS, Mueller C, Kamiyama N, Saiga H. 125.  et al. 2011. ATF6-beta is a host cellular target of the Toxoplasma gondii virulence factor ROP18. J. Exp. Med. 208:1533–46 [Google Scholar]
  126. Yamamoto M, Okuyama M, Ma JS, Kimura T, Kamiyama N. 126.  et al. 2012. A cluster of interferon-γ-inducible p65 GTPases plays a critical role in host defense against Toxoplasma gondii. Immunity 37:302–13 [Google Scholar]
  127. Yamamoto M, Standley DM, Takashima S, Saiga H, Okuyama M. 127.  et al. 2009. A single polymorphic amino acid on Toxoplasma gondii kinase ROP16 determines the direct and strain-specific activation of Stat3. J. Exp. Med. 206:2747–60 [Google Scholar]
  128. Yap GS, Sher A. 128.  1999. Effector cells of both nonhemopoietic and hemopoietic origin are required for interferon (IFN)-γ– and tumor necrosis factor (TNF)-α–dependent host resistance to the intracellular pathogen, Toxoplasma gondii. J. Exp. Med. 189:1083–91 [Google Scholar]
  129. Zhao Y, Ferguson DJ, Wilson DC, Howard JC, Sibley LD, Yap GS. 129.  2009. Virulent Toxoplasma gondii evade immunity-related GTPase-mediated parasite vacuole disruption within primed macrophages. J. Immunol. 182:3775–81 [Google Scholar]
  130. Zhao Z, Fux B, Goodwin M, Dunay IR, Strong D. 130.  et al. 2008. Autophagosome-independent essential function for the autophagy protein Atg5 in cellular immunity to intracellular pathogens. Cell Host Microbe 4:458–69 [Google Scholar]
  131. Zhou P, Nie H, Zhang LX, Wang HY, Yin CC. 131.  et al. 2010. Genetic characterization of Toxoplasma gondii isolates from pigs in China. J. Parasitol. 96:1027–29 [Google Scholar]

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