Core - Preparation, Supply of Toxoplasma and Immunologicals

Araujo, Fausto

Abstract

In the present grant proposal the individual projects are designed to examine the activity of new therapeutic agents against T. gondii, to investigate new enzymatic pathways that may prove important for design of drugs active against the parasite and to identify and characterize the genes of the organism that are responsible for drug resistance. The ultimate objectives are to identify more active and safer therapeutic agents for treatment of toxoplasmosis, particularly toxoplasmic encephalitis in AIDS patients. For each of the proposed studies, tachyzoites, cysts and bradyzoites of different strains of T. gondii will be needed in large numbers. Tachyzoites and cysts will be used for infection of mice and of mammalian cells in tissue culture for in vivo and in vitro evaluation of the activity of therapeutic agents against T. gondii. Tachyzoite and bradyzoites will also be used to investigate biochemical and metabolic pathways which may prove to be useful as targets for inactivation or inhibition by therapeutic agents. These forms of T. gondii will be provided by this Core. In addition, this Core will also provide antisera to T. gondii for use in serological and immunochemical assays and antisera to IFN-gamma for use un preparation of tachyzoites of strains of T. gondii of low virulence for mice.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Allergy and Infectious Diseases (NIAID)
• Type: Research Project--Cooperative Agreements (U01)
• Project #: 5U01AI030230-05
• Application #: 3727291
• Support Year: 5
• Fiscal Year: 1995

Institution

• Name: Palo Alto Medical Foundation Research Institute
• DUNS #: 622276137
• City: Palo Alto
• State: CA
• Country: United States
• Zip Code: 94301

Publications

Saeij, J P J; Boyle, J P; Coller, S et al. (2006) Polymorphic secreted kinases are key virulence factors in toxoplasmosis. Science 314:1780-3

McFadden, D C; Tomavo, S; Berry, E A et al. (2000) Characterization of cytochrome b from Toxoplasma gondii and Q(o) domain mutations as a mechanism of atovaquone-resistance. Mol Biochem Parasitol 108:12-Jan

Liesenfeld, O; Kang, H; Park, D et al. (1999) TNF-alpha, nitric oxide and IFN-gamma are all critical for development of necrosis in the small intestine and early mortality in genetically susceptible mice infected perorally with Toxoplasma gondii. Parasite Immunol 21:365-76

McFadden, D C; Boothroyd, J C (1999) Cytochrome b mutation identified in a decoquinate-resistant mutant of Toxoplasma gondii. J Eukaryot Microbiol 46:81S-82S

Boothroyd, J C; Hehl, A; Knoll, L J et al. (1998) The surface of Toxoplasma: more and less. Int J Parasitol 28:3-9

Black, M W; Boothroyd, J C (1998) Development of a stable episomal shuttle vector for Toxoplasma gondii. J Biol Chem 273:3972-9

Neyer, L E; Kang, H; Remington, J S et al. (1998) Mesenteric lymph node T cells but not splenic T cells maintain their proliferative response to concanavalin-A following peroral infection with Toxoplasma gondii. Parasite Immunol 20:573-81

Manger, I D; Hehl, A B; Boothroyd, J C (1998) The surface of Toxoplasma tachyzoites is dominated by a family of glycosylphosphatidylinositol-anchored antigens related to SAG1. Infect Immun 66:2237-44

Manger, I D; Hehl, A; Parmley, S et al. (1998) Expressed sequence tag analysis of the bradyzoite stage of Toxoplasma gondii: identification of developmentally regulated genes. Infect Immun 66:1632-7

Subauste, C S; Fuh, F; de Waal Malefyt, R et al. (1998) Alpha beta T cell response to Toxoplasma gondii in previously unexposed individuals. J Immunol 160:3403-11