Cluster of four surface antigen genes specifically expressed in bradyzoites, SAG2CDXY, plays an important role in persistence

Infect Immun. 2008 Mar 17 [Epub ahead of print]

A cluster of four surface antigen genes specifically expressed in bradyzoites, SAG2CDXY, plays an important role in Toxoplasma gondii persistence

Saeij JP, Arrizabalaga G, Boothroyd JC.

Stanford University School of Medicine, Department of Microbiology and Immunology, Stanford, CA 94305.

Toxoplasma gondii is one of the most successful protozoan parasites of warm-blooded animals. Key to its ability to establish a chronic infection in immunocompetent animals is thought to be stage-specific expression of its surface molecules. The rapidly dividing tachyzoite stage displays a different subset of the family of surface antigen-1 (SAG1)-related-sequences (SRS) compared to 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 found in the brain, where cysts develop, or 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 bioluminescent imaging (BLI) 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 element(s) that normally suppress expression in tachyzoites. Comparing mice infected with wild-type or mutants 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.

PMID: 18347037 [PubMed - as supplied by publisher]