A transmembrane domain containing pellicle protein of Toxoplasma gondii enhances virulence and invasion after extracellular stress.

To identify Toxoplasma gondii genes important in the establishment of a persistent infection, we previously used signature-tagged mutagenesis to identify mutants with reduced cyst numbers in the brains of mice. One of the mutants, 95C5, has an insertion within a predicted six transmembrane domain protein, which localizes to the parasite pellicle, thus we named it transmembrane pellicle protein 1 (TgTPP1). Although the 95C5 mutant was found be reduced in its ability to form brain cysts, it is defective during acute infection. Addition of TgTPP1 expressed from its endogenous promoter restored the acute lethality of the 95C5 mutant to parental levels. The 95C5 mutant does not have a growth defect in standard tissue culture conditions; however, we found a significant defect in host cell penetration after extracellular stress. Overall, TgTPP1 may function during acute infection by enhancing the parasites ability to invade after extracellular stress.