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Disease relevance of Toxoplasma


High impact information on Toxoplasma

  • We investigated the response to infection with Toxoplasma gondii in Ucp2-/- mice, and found that they are completely resistant to infection, in contrast with the lethality observed in wild-type littermates [6].
  • CD resistance in Toxoplasma was mediated by a point mutation in the single-copy actin gene ACT1 [7].
  • De novo pyrimidine biosynthesis is required for virulence of Toxoplasma gondii [8].
  • A system for stable transformation of Toxoplasma gondii tachyzoites was developed that exploited the susceptibility of Toxoplasma to chloramphenicol [9].
  • The fact that an antibody to interferon-gamma can eliminate resistance to acute Toxoplasma infection in mice suggests that this lymphokine is an important mediator of host resistance to this parasite [10].

Chemical compound and disease context of Toxoplasma


Biological context of Toxoplasma


Anatomical context of Toxoplasma


Associations of Toxoplasma with chemical compounds

  • Gene replacement in Toxoplasma gondii with chloramphenicol acetyltransferase as selectable marker [9].
  • The activities of the endogenous O2- and H2O2 scavenging enzymes, superoxide dismutase (SOD), glutathionine peroxidase (GP), and catalase, were measured in lysates of the intracellular parasite, Toxoplasma gondii, and in various macrophage populations [25].
  • Human platelet-mediated cytotoxicity against Toxoplasma gondii: role of thromboxane [26].
  • Quenching OH. and 1O2, presumed products of O2--H2O2 interaction, by mannitol, benzoate, diazabicyclooctane, and histidine, also inhibited toxoplasma killing by xanthine-xanthine oxidase [27].
  • In vitro activation of resident and chemically-elicited cells by 72 h of exposure to mitogen- and antigen-prepared lymphokines, conditions that induce trypanocidal (5) and leishmanicidal activity (14), stimulated O2- and H2O2 release, and enhanced nitroblue tetrazolium reduction in response to toxoplasma ingestion [28].

Gene context of Toxoplasma

  • We used this information to search for other rhomboid substrates and identified a family of adhesion proteins from the human parasite Toxoplasma gondii, the TMDs of which were efficient substrates for rhomboid proteases [29].
  • Mice lacking the transcription factor interferon consensus sequence binding protein (ICSBP), a member of the interferon regulatory factor family of transcription proteins, were infected with the intracellular protozoan, Toxoplasma gondii [30].
  • Inhibition of HIV-1 infection by a CCR5-binding cyclophilin from Toxoplasma gondii [31].
  • This study describes the use of rapid transient kinetic methods to characterize the bifunctional thymidylate synthase-dihydrofolate reductase (TS-DHFR) enzyme from Toxoplasma gondii [32].
  • These results illustrate that in Toxoplasma encephalitis, TNF-alpha-mediated immune responses are of crucial importance and that signaling through TNFR1, but not TNFR2, provides the stimulus required for the induction of protective nitric oxide [33].

Analytical, diagnostic and therapeutic context of Toxoplasma

  • Here we show that ligation of the C-C chemokine receptor (CCR) 5 can provide a major signal for the induction of IL-12 synthesis by the CD8 alpha+ subset of DC and that this pathway is important in establishing interferon gamma-dependent resistance to the protozoan parasite Toxoplasma gondii [34].
  • Additionally, eosin B was found to be a 180 microm inhibitor of Toxoplasma gondii in both biochemical and cell culture assays [35].
  • Western Blot analysis revealed that both IgM and IgG antibodies present in the sera of humans infected with Toxoplasma gondii recognize three major antigens with apparent m.w. of 32,000, 22,000, and 6000, respectively [36].
  • The first part of this work presents the sequence of the first 20 NH2 terminus residues obtained from P30, the major surface Ag of Toxoplasma gondii, purified by HPLC [37].
  • A polysaccharide fraction from Toxoplasma gondii was adsorbed to polystyrene plates, and the enzyme-linked immunosorbent assay was performed (poly-ELISA) with peroxidase-labeled anti-immunoglobulin G and anti-immunoglobulin M antibodies [38].


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  2. The Exocytosis-regulatory protein synaptotagmin VII mediates cell invasion by Trypanosoma cruzi. Caler, E.V., Chakrabarti, S., Fowler, K.T., Rao, S., Andrews, N.W. J. Exp. Med. (2001) [Pubmed]
  3. Potent in vitro and in vivo antitoxoplasma activity of the lipid-soluble antifolate trimetrexate. Allegra, C.J., Kovacs, J.A., Drake, J.C., Swan, J.C., Chabner, B.A., Masur, H. J. Clin. Invest. (1987) [Pubmed]
  4. Clindamycin for toxoplasma encephalitis in AIDS. Remington, J.S., Vildé, J.L. Lancet (1991) [Pubmed]
  5. A novel triterpenoid induces transforming growth factor beta production by intraepithelial lymphocytes to prevent ileitis. Minns, L.A., Buzoni-Gatel, D., Ely, K.H., Rachinel, N., Luangsay, S., Kasper, L.H. Gastroenterology (2004) [Pubmed]
  6. Disruption of the uncoupling protein-2 gene in mice reveals a role in immunity and reactive oxygen species production. Arsenijevic, D., Onuma, H., Pecqueur, C., Raimbault, S., Manning, B.S., Miroux, B., Couplan, E., Alves-Guerra, M.C., Goubern, M., Surwit, R., Bouillaud, F., Richard, D., Collins, S., Ricquier, D. Nat. Genet. (2000) [Pubmed]
  7. Toxoplasma invasion of mammalian cells is powered by the actin cytoskeleton of the parasite. Dobrowolski, J.M., Sibley, L.D. Cell (1996) [Pubmed]
  8. De novo pyrimidine biosynthesis is required for virulence of Toxoplasma gondii. Fox, B.A., Bzik, D.J. Nature (2002) [Pubmed]
  9. Gene replacement in Toxoplasma gondii with chloramphenicol acetyltransferase as selectable marker. Kim, K., Soldati, D., Boothroyd, J.C. Science (1993) [Pubmed]
  10. Interferon-gamma: the major mediator of resistance against Toxoplasma gondii. Suzuki, Y., Orellana, M.A., Schreiber, R.D., Remington, J.S. Science (1988) [Pubmed]
  11. Prophylaxis for opportunistic infections in patients with HIV infection. Gallant, J.E., Moore, R.D., Chaisson, R.E. Ann. Intern. Med. (1994) [Pubmed]
  12. Low-dose trimethoprim-sulfamethoxazole prophylaxis for toxoplasmic encephalitis in patients with AIDS. Carr, A., Tindall, B., Brew, B.J., Marriott, D.J., Harkness, J.L., Penny, R., Cooper, D.A. Ann. Intern. Med. (1992) [Pubmed]
  13. Primary prophylaxis for Pneumocystis carinii pneumonia: a randomized trial comparing cotrimoxazole, aerosolized pentamidine and dapsone plus pyrimethamine. Mallolas, J., Zamora, L., Gatell, J.M., Miró, J.M., Vernet, E., Valls, M.E., Soriano, E., SanMiguel, J.G. AIDS (1993) [Pubmed]
  14. Assessment of therapy for toxoplasma encephalitis. The TE Study Group. Haverkos, H.W. Am. J. Med. (1987) [Pubmed]
  15. Effects of drug therapy on Toxoplasma cysts in an animal model of acute and chronic disease. Gormley, P.D., Pavesio, C.E., Minnasian, D., Lightman, S. Invest. Ophthalmol. Vis. Sci. (1998) [Pubmed]
  16. A role for CD4+ NK1.1+ T lymphocytes as major histocompatibility complex class II independent helper cells in the generation of CD8+ effector function against intracellular infection. Denkers, E.Y., Scharton-Kersten, T., Barbieri, S., Caspar, P., Sher, A. J. Exp. Med. (1996) [Pubmed]
  17. Oxygen-independent killing by alveolar macrophages. Catterall, J.R., Sharma, S.D., Remington, J.S. J. Exp. Med. (1986) [Pubmed]
  18. Association of CD4+ T cell-dependent, interferon-gamma-mediated necrosis of the small intestine with genetic susceptibility of mice to peroral infection with Toxoplasma gondii. Liesenfeld, O., Kosek, J., Remington, J.S., Suzuki, Y. J. Exp. Med. (1996) [Pubmed]
  19. The Toxoplasma gondii protein MIC3 requires pro-peptide cleavage and dimerization to function as adhesin. Cérède, O., Dubremetz, J.F., Bout, D., Lebrun, M. EMBO J. (2002) [Pubmed]
  20. IP-10 is critical for effector T cell trafficking and host survival in Toxoplasma gondii infection. Khan, I.A., MacLean, J.A., Lee, F.S., Casciotti, L., DeHaan, E., Schwartzman, J.D., Luster, A.D. Immunity (2000) [Pubmed]
  21. Identification of interferon-gamma as the lymphokine that activates human macrophage oxidative metabolism and antimicrobial activity. Nathan, C.F., Murray, H.W., Wiebe, M.E., Rubin, B.Y. J. Exp. Med. (1983) [Pubmed]
  22. Interleukin-12, dendritic cells, and the initiation of host-protective mechanisms against Toxoplasma gondii. Johnson, L.L., Sayles, P.C. J. Exp. Med. (1997) [Pubmed]
  23. Inhibition of cytoplasmic and organellar protein synthesis in Toxoplasma gondii. Implications for the target of macrolide antibiotics. Beckers, C.J., Roos, D.S., Donald, R.G., Luft, B.J., Schwab, J.C., Cao, Y., Joiner, K.A. J. Clin. Invest. (1995) [Pubmed]
  24. CCR5 mediates specific migration of Toxoplasma gondii-primed CD8 lymphocytes to inflammatory intestinal epithelial cells. Luangsay, S., Kasper, L.H., Rachinel, N., Minns, L.A., Mennechet, F.J., Vandewalle, A., Buzoni-Gatel, D. Gastroenterology (2003) [Pubmed]
  25. Macrophage oxygen-dependent antimicrobial activity. IV. Role of endogenous scavengers of oxygen intermediates. Murray, H.W., Nathan, C.F., Cohn, Z.A. J. Exp. Med. (1980) [Pubmed]
  26. Human platelet-mediated cytotoxicity against Toxoplasma gondii: role of thromboxane. Yong, E.C., Chi, E.Y., Fritsche, T.R., Henderson, W.R. J. Exp. Med. (1991) [Pubmed]
  27. Macrophage oxygen-dependent antimicrobial activity. I. Susceptibility of Toxoplasma gondii to oxygen intermediates. Murray, H.W., Cohn, Z.A. J. Exp. Med. (1979) [Pubmed]
  28. Macrophage oxygen-dependent antimicrobial activity. III. Enhanced oxidative metabolism as an expression of macrophage activation. Murray, H.W., Cohn, Z.A. J. Exp. Med. (1980) [Pubmed]
  29. Substrate specificity of rhomboid intramembrane proteases is governed by helix-breaking residues in the substrate transmembrane domain. Urban, S., Freeman, M. Mol. Cell (2003) [Pubmed]
  30. Interferon consensus sequence binding protein-deficient mice display impaired resistance to intracellular infection due to a primary defect in interleukin 12 p40 induction. Scharton-Kersten, T., Contursi, C., Masumi, A., Sher, A., Ozato, K. J. Exp. Med. (1997) [Pubmed]
  31. Inhibition of HIV-1 infection by a CCR5-binding cyclophilin from Toxoplasma gondii. Golding, H., Aliberti, J., King, L.R., Manischewitz, J., Andersen, J., Valenzuela, J., Landau, N.R., Sher, A. Blood (2003) [Pubmed]
  32. Mechanistic characterization of Toxoplasma gondii thymidylate synthase (TS-DHFR)-dihydrofolate reductase. Evidence for a TS intermediate and TS half-sites reactivity. Johnson, E.F., Hinz, W., Atreya, C.E., Maley, F., Anderson, K.S. J. Biol. Chem. (2002) [Pubmed]
  33. Crucial role of TNF receptor type 1 (p55), but not of TNF receptor type 2 (p75), in murine toxoplasmosis. Deckert-Schlüter, M., Bluethmann, H., Rang, A., Hof, H., Schlüter, D. J. Immunol. (1998) [Pubmed]
  34. CCR5 provides a signal for microbial induced production of IL-12 by CD8 alpha+ dendritic cells. Aliberti, J., Reis e Sousa, C., Schito, M., Hieny, S., Wells, T., Huffnagle, G.B., Sher, A. Nat. Immunol. (2000) [Pubmed]
  35. A molecular docking strategy identifies Eosin B as a non-active site inhibitor of protozoal bifunctional thymidylate synthase-dihydrofolate reductase. Atreya, C.E., Johnson, E.F., Irwin, J.J., Dow, A., Massimine, K.M., Coppens, I., Stempliuk, V., Beverley, S., Joiner, K.A., Shoichet, B.K., Anderson, K.S. J. Biol. Chem. (2003) [Pubmed]
  36. Western Blot analysis of the antigens of Toxoplasma gondii recognized by human IgM and IgG antibodies. Sharma, S.D., Mullenax, J., Araujo, F.G., Erlich, H.A., Remington, J.S. J. Immunol. (1983) [Pubmed]
  37. Protection of mice and nude rats against toxoplasmosis by a multiple antigenic peptide construction derived from Toxoplasma gondii P30 antigen. Darcy, F., Maes, P., Gras-Masse, H., Auriault, C., Bossus, M., Deslee, D., Godard, I., Cesbron, M.F., Tartar, A., Capron, A. J. Immunol. (1992) [Pubmed]
  38. Enzyme-linked immunosorbent assay for antibodies to Toxoplasma gondii polysaccharides in human toxoplasmosis. Mineo, J.R., Camargo, M.E., Ferreira, A.W. Infect. Immun. (1980) [Pubmed]
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