title: A cluster of four surface antigen genes specifically expressed in bradyzoites, SAG2CDXY, plays an important role in Toxoplasma gondii persistence.
abstract: Toxoplasma gondii is one of the most successful protozoan parasites of warm-blooded animals. Stage-specific expression of its surface molecules is thought to be key to its ability to establish chronic infection in immunocompetent animals. The rapidly dividing tachyzoite stage displays a different subset of family of surface antigen 1 (SAG1)-related sequences (SRSs) from that displayed by the encysted bradyzoite stage. It is possible that this switch is necessary to protect the bradyzoites against an immune response raised against the tachyzoite stage. Alternatively, it might be that bradyzoite SRSs evolved to facilitate invasion of different cell types, such as those found in the brain, where cysts develop, or the small intestine, where bradyzoites must enter after oral infection. Here we studied the function of a cluster of four tandem genes, encoding bradyzoite SRSs called SAG2C, -D, -X, and -Y. Using bioluminescence imaging of mice infected with parasites expressing firefly luciferase (FLUC) driven by the SAG2D promoter, we show stage conversion for the first time in living animals. A truncated version of the SAG2D promoter (SAG2Dmin) gave efficient expression of FLUC in both tachyzoites and bradyzoites, indicating that the bradyzoite specificity of the complete SAG2D promoter is likely due to an element(s) that normally suppresses expression in tachyzoites. Comparing mice infected with the wild type or a mutant where the SAG2CDXY cluster of genes has been deleted (DeltaSAG2CDXY), we demonstrate that whereas DeltaSAG2CDXY parasites are less capable of maintaining a chronic infection in the brain, they do not show a defect in oral infectivity.
authors.affiliation: Stanford University School of Medicine, Department of Microbiology and Immunology, Stanford, CA 94305-5124, USA.
authors.forename: Jeroen P J
authors.initials: JP
authors.lastname: Saeij
authors.forename: Gustavo
authors.initials: G
authors.lastname: Arrizabalaga
authors.forename: John C
authors.initials: JC
authors.lastname: Boothroyd
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics*; D000954:Antigens, Surface / Q000235:genetics; D001921:Brain / Q000469:parasitology; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D017125:Genes, Protozoan / Q000502:physiology*; D008168:Lung / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D005810:Multigene Family / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000502:physiology; D015800:Protozoan Proteins / Q000235:genetics*; D014122:Toxoplasma / Q000235:genetics* / Q000276:immunology; D014124:Toxoplasmosis, Animal / Q000469:parasitology*
chemical_list: D000953:Antigens, Protozoan; D000954:Antigens, Surface; D015800:Protozoan Proteins; C067547:surface antigen P22, Toxoplasma