Proteotyping reactivant toxoplasmic encephalitis reveals virulence-associated dense granule protein GRA5 polymorphisms.

BACKGROUND

A fatal case of toxoplasmic encephalitis has caused microbiologists and clinicians to question whether different strains of Toxoplasma gondii have more pathogenic potential than others. This is concerning, as T. gondii is a widely spread parasite presumed to lie dormant in a third of the world's population.

METHODS

Here, we expand on a previous proteomic analysis of toxoplasmosis and have identified T. gondii-specific peptides in the cerebrospinal fluid (CSF) of three cases of toxoplasmic reactivation. Multilocus PCR-restriction fragment-length polymorphism (PCR-RFLP) genetically identified the T. gondii strain responsible for a fatal case as ToxoDB PCR-RFLP genotype #7. Using other T. gondii strains of this genotype, we performed bioassays to compare the pathogenicity of this genotype to the Type II strain, ME49.

RESULTS

Both tested genotype #7 strains have greater pathogenic potential, although likely through different mechanisms. Of the most abundant T. gondii-specific CSF peptides across multiple patients, we identified a polymorphic region of the dense granule protein GRA5 with strain specificity.

CONCLUSIONS

This approach could represent a "proteotype" that allows for T. gondii strain identification. Ultimately, CSF could be a valuable tool for distinguishing strains among T. gondii-exposed individuals with toxoplasmic encephalitis and may prove useful for future identification of the presence of T. gondii in clinically silent patients.