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Genetic Basis of Pathogenicity in Toxoplasmosis

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Toxoplasma gondii

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 219))

Abstract

Toxoplasma gondii is among the most prevalent chronic parasitic infections in humans, infecting from 10% to 25% of the world’s population (Dubey and Beattie 1988). While infections are often benign, toxoplasmosis has emerged as an important opportunistic pathogen in immunocompromised patients. The identification of virulence factors is complicated by the fact that disease is rarely overt in the healthy host. This problem is amplified by the unusual population structure of T. gondii that results in coinheritance of many unlinked loci. Despite these complications, it is important to identify specific parasite components that contribute to pathology as they provide predictive markers of disease progression and may identify potential targets for intervention. The recent advent of genetic tools for use in protozoan parasites enables direct molecular identification of virulence determinants. This new-found technology also obligates investigators to a higher standard in establishing the molecular basis of virulence. This review provides a framework for the application of molecular genetics to investigate pathogenicity of toxoplasmosis.

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References

  • Araujo FG, Williams OM, Grumet FC, Remington JS (1976) Strain-dependent differences in murine susceptibility to Toxoplasma. Infect Immun 13: 1528–1530

    PubMed  CAS  Google Scholar 

  • Boothroyd JC, Black M, Kim K, Pfefferkorn ER, Seeber F, Sibley LO, Soldati O (1995). Forward and reverse genetics in the study of the obligate, intracellular parasite Toxoplasma gondii. In: Adolph K (ed) Methods in molecular genetics. Academic, New York, pp 3–29

    Google Scholar 

  • Brown C, McLeod R (1994) Mechanisms of survival of mice during acute and chronic Toxoplasma gondii infection. Parasitol Today 10:290–292

    Article  PubMed  CAS  Google Scholar 

  • Bulow R, Boothroyd JC (1991) Protection of mice from fatal Toxoplasma infection by immunization with P30 antigen in liposomes. J Immunol 147:3496–3500

    PubMed  CAS  Google Scholar 

  • Burg JL, Perlman D, Kasper LH, Ware PL, Boothroyd JC (1988) Molecular analysis of the gene encoding the major surface antigen of Toxoplasma gondii. J Immunol 141:3584–3591

    PubMed  CAS  Google Scholar 

  • Cornelissen AWCA, Overdulve JP (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. Parasitol 90:35–44

    Article  Google Scholar 

  • Cornelissen AWCA, Overdulve JP Van der Ploeg, M (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. Parasitol 88:531–553

    Article  CAS  Google Scholar 

  • Couvreur G, Sadak A, Fortier B, Dubremetz JF (1988) Surface antigens of Toxoplasma gondii. Parasitol 97:1–10

    Article  Google Scholar 

  • Cristina N, Oury P, Ambroise-Thomas P, Santoro F (1991) Restriction fragment length polymorphisms among Toxoplasma gondii strains. Parasitol Res 77:266–268

    Article  PubMed  CAS  Google Scholar 

  • Cristina N, DardĂ© ML, Boudin C, Tavernier G, Pestre-Alexandre M, Ambroise-Thomas P (1995) A DNA fingerprinting method for individual characterization of Toxoplasma gondii strains: combination with isoenzymatic characters for determination of linkage groups. Parasitol Res 81:32–37

    Article  PubMed  CAS  Google Scholar 

  • DardĂ© ML, Bouteille B, Pestre-Alexandre M (1992) Isoenzyme analysis of 35 Toxoplasma gondii isolates: biological and epidemiological implications. J Parasitol 78:786–794

    Article  PubMed  Google Scholar 

  • Derouin F, Garin YJF (1991) Toxoplasma gondii: blood and tissue kinetics during acute and chronic infections in mice. Exp Parasitol 73:460–468

    Article  PubMed  CAS  Google Scholar 

  • Desmonts G, Couvreur J (1974) Congenital toxoplasmosis: a prospective study of 378 pregnancies. N Engl J Med 290:1110–1116

    Article  PubMed  CAS  Google Scholar 

  • Donald RGK, Roos DS (1994) Homologous recombination and gene replacement at the dihydrofolate reductase-thymidylate synthase locus in Toxoplasma gondii. Mol Biochem Parasitol 63:243–253

    Article  PubMed  CAS  Google Scholar 

  • Donald RGK, Roos DS (1995) Insertional mutagenesis and marker rescue in a protozoan parasite: cloning of the uracil phosphoribosyl transferase locus from Toxoplasma gondii. Proc Natl Acad Sci 92:5749–5753

    Article  PubMed  CAS  Google Scholar 

  • Dubey JP (1977) Toxoplasma. Hammondia. Besnoitia. Sarcocystis. and other tissue cyst-forming coccidia of man and animals. In: Kreier JP (ed) Parasitic Protozoa. Academic. New York. pp 101–237

    Google Scholar 

  • Dubey J (1980) Mouse pathogenicity of Toxoplasma gondii isolated from a goat. Am J Vet Res 41:427–429

    PubMed  CAS  Google Scholar 

  • Dubey JP (1992) Isolation of Toxoplasma gondii from a naturally infected beef cow. J Parasitol 78:151–153

    Article  PubMed  CAS  Google Scholar 

  • Dubey JP, Beattie CP (1988) Toxoplasmosis of animals and man. CRC, Boca Raton

    Google Scholar 

  • Dubey JP, Frenkel, JF (1972) Cyst-induced toxoplasmosis in cats. J Protozool 19:155–177

    PubMed  CAS  Google Scholar 

  • Frenkel JK (1988) Pathophysiology of toxoplasmosis. Parasitol Today 4:273–278

    Article  PubMed  CAS  Google Scholar 

  • Frenkel JK, Escajadillo A (1987) Cyst rupture as a pathogenic mechanism of toxoplasmic encephalitis. Am J Trop Med Hyg 36:517–522

    PubMed  CAS  Google Scholar 

  • Frenkel JK, Smith DD (1982) Immunization of cats against shedding of Toxoplasma oocysts. J Parasitol 68:744–748

    Article  PubMed  CAS  Google Scholar 

  • Gazzinelli RT, Eltoum I, Wynn TA, Sher A (1993) Acute cerebral toxoplasmosis is induced by in vivo neutralization of TNF-a and correlates with the down-regulated expression of inducible nitric oxide synthase and other markers of macrophage activation. J Immunol 151:3672–3681

    PubMed  CAS  Google Scholar 

  • Handman E, Goding JW, Remington JS (1980) Detection and characterization of membrane antigens of Toxoplasma gondii. J Immunol 124:2578–2583

    PubMed  CAS  Google Scholar 

  • Howe DK, Sibley LD (1994) Toxoplasma gondii: analysis of different laboratory stocks of RH strain reveals genetic heterogeneity. Exp Parasitol 78:242–245

    Article  PubMed  CAS  Google Scholar 

  • Howe DK, Sibley LD (1995) Toxoplasma gondii is comprised of three clonal lineages: correlation of parasite genotype with human disease. J Infect Dis 172:1561–1566

    Article  PubMed  CAS  Google Scholar 

  • Hunter CA, Roberts CW, Alexander J (1992) Kinetics of cytokine mRNA production in the brains of mice with progressive toxoplasmic encephalitis. Eur J Immunol 22:2317–2322

    Article  PubMed  CAS  Google Scholar 

  • Israelski DM, Remington JS (1993) Toxoplasmosis in the non-AIDS immunocompromised host. Curr Clin Top Infect Dis 13:322–356

    PubMed  CAS  Google Scholar 

  • Kasper LH, Ware PL (1985) Recognition and characterization of stage-specific oocyst/sporozoite antigens of Toxoplasma gondii by human antisera. J Clin Invest 75: 1570–1577

    Article  PubMed  CAS  Google Scholar 

  • Kim K, Soldati D, Boothroyd JC (1993) Gene replacement in Toxoplasma gondii with chloramphenicol acetyltransferase as selectable marker. Science 262:911–914

    Article  PubMed  CAS  Google Scholar 

  • Krahenbuhl JL, Remington JS (1982) The immunology of Toxoplasma and toxoplasmosis. In: Cohen S. Warren KS (eds) Immunology of parasitic infections. Blackwell London. pp 356–421

    Google Scholar 

  • Luft BJ, Remington JS (1992) Toxoplasmic encephalitis in AIDS. Clin Infect Dis 15:211–222

    Article  PubMed  CAS  Google Scholar 

  • McLeod R, Eisenhauer P, Mack D, Brown C, Filice G, Spitalny G (1989a) Immune responses associated with early survival after peroral infection with Toxoplasma gondii. J Immunol 142:3247–3255

    PubMed  CAS  Google Scholar 

  • McLeod R, Skamene E, Brown CR, Eisenhauer PB, Mack DG (1989b) Genetic regulation of early survival and cyst number after peroral Toxoplasma gondii infection of AXB/BXA recombinant inbred and congenic mice. J Immunol 143:3031–3034

    PubMed  CAS  Google Scholar 

  • Parmley SF, Gross U, Sucharczuk A, Windeck T, Sgarlato GD, Remington JS (1994) Two alleles of the gene encoding surface antigen P22 in 25 strains of Toxoplasma gondii. J Parasitol 80:293–301

    Article  PubMed  CAS  Google Scholar 

  • Pfefferkorn ER, Pfefferkorn LC, Colby ED (1977) Development of gametes and oocysts in cats fed cysts derived from cloned trophozoites of Toxoplasma gondii. J Parasitol 63: 158–159

    Article  PubMed  CAS  Google Scholar 

  • Pfefferkorn LC, Pfefferkorn ER (1980) Toxoplasma gondii: Genetic recombination between drug resistant mutants. Exp Parasitol 50:305–316

    Article  PubMed  CAS  Google Scholar 

  • Reikvam S, Lorentzen-Styr AM (1976) Virulence of different strains of Toxoplasma gondii and host response in mice. Nature 261:508–509

    Article  PubMed  CAS  Google Scholar 

  • Remington JS, Jacobs L, Melton M (1961) Congenital transmission of toxoplasmosis from mother animals with acute and chronic infections. J Infect Dis 108:163–173

    Article  PubMed  CAS  Google Scholar 

  • Roos DS, Donald RGK, Morrissette NS, Moulton AL (1994) Molecular tools for genetic dissection of the protozoan parasite Toxoplasma gondii. Meth Cell Biol 45:28–61

    Google Scholar 

  • Sibley LD, Boothroyd JC (1992) Virulent strains of Toxoplasma gondii comprise a single clonal lineage. Nature 359:82–85

    Article  PubMed  CAS  Google Scholar 

  • Sibley LD, LeBlanc AJ, Pfefferkorn ER, Boothroyd JC (1992) Generation of a restriction fragment length polymorphism linkage map for Toxoplasma gondii. Genetics 132: 1003–1015

    PubMed  CAS  Google Scholar 

  • Sibley LD, Howe DK, Wan KL, Khan S, Aslett M, Ajioka J (1995). Toxoplasma gondii as a model genetic system. In: Smith D, Parsons M (eds) Molecular biology of parasitic protozoa. Oxford University, Cambridge

    Google Scholar 

  • Smith JM, Smith NH, O’Rouke M, Spratt BG (1993) How clonal are bacteria? Proc Natl Acad Sci 90:4384–4388

    Article  PubMed  CAS  Google Scholar 

  • Sumyuen MH, Garin YJF, Derouin F (1995) Early kinetics of Toxoplasma gondii infection in mice orally infected with cysts of an avirulent strain. J Parasitol 81:327–329

    Article  PubMed  CAS  Google Scholar 

  • Suzuki Y, Joh K (1994) Effect of the strain of Toxoplasma gondii on the development of toxoplasmic encephalitis in mice treated with antibody to interferon-Îł. Parasitol Res 80: 125–130

    Article  PubMed  CAS  Google Scholar 

  • Suzuki Y, Conley FK, Remington JS (1989) Differences in virulence and development of encephalitis during chronic infection vary with the strain of Toxoplasma gondii. J Infect Dis 159:790–794

    Article  PubMed  CAS  Google Scholar 

  • Suzuki Y, Joh K, Orellana MA, Conley FK, Remington JS (1991) A gene(s) within the H-2D region determines the development of toxoplasmic encephalitis in mice. Immunol 74:732–739

    CAS  Google Scholar 

  • Suzuki Y, Orellana MA, Wong SY, Conley FK, Remington JS (1993) Susceptibility to chronic infection with Toxoplasma gondii does not correlate with susceptibility to acute infection in mice. Infect Immun 61:2284–2288

    PubMed  CAS  Google Scholar 

  • Tibayrenc M, Ayala FJ (1991) Towards a population genetics of microorganisms: the clonal theory of parasitic protozoa. Parasitol Today 7:228–235

    Article  PubMed  CAS  Google Scholar 

  • Tibayrenc M, Kjellberg F, Araud J, Oury B, Breniere SF, DardĂ© ML, Ayala FJ (1991) Are eukaryotic microorganisms clonal or sexual? A population genetics vantage. Proc Natl Acad Sci 88:5129–5133

    Article  PubMed  CAS  Google Scholar 

  • Tibayrenc M, Kjellberg F, Ayala FJ (1990) A clonal theory of parasitic protozoa: the population structures of Entamoeba, Giardia, Leishmania, Naegleria, Plasmodium, Trichomonas, and Trypanosoma and their medical and taxonomic consequences. Proc Natl Acad Sci 87:2414–2418

    Article  PubMed  CAS  Google Scholar 

  • Williams DM, Grumet FC, Remington JS (1978) Genetic control of murine resistance to Toxoplasma gondii. Infect Immun 19:416–420

    PubMed  CAS  Google Scholar 

  • Wong S, Remington JS (1994) Toxoplasmosis in pregnancy. Clin Infect Dis 18:853–862

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, 63110, USA

    L. D. Sibley & D. K. Howe

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  1. L. D. Sibley
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  2. D. K. Howe
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Editors and Affiliations

  1. Institute for Hygiene and Microbiology, University of WĂĽrzburg, Josef-Schneider-Str. 2, D-97080, WĂĽrzburg, Germany

    Uwe Gross

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© 1996 Springer-Verlag Berlin Heidelberg

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Sibley, L.D., Howe, D.K. (1996). Genetic Basis of Pathogenicity in Toxoplasmosis. In: Gross, U. (eds) Toxoplasma gondii. Current Topics in Microbiology and Immunology, vol 219. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-51014-4_1

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  • DOI: https://doi.org/10.1007/978-3-642-51014-4_1

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-51016-8

  • Online ISBN: 978-3-642-51014-4

  • eBook Packages: Springer Book Archive

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