Genetic basis for phenotypic differences between different Toxoplasma gondii type I strains

Area of Science:

• Parasitology
• Genomics
• Immunology

Background:

• Toxoplasma gondii exhibits clonal populations in North America and Europe, with types I, II, and III being predominant.
• The type I strain RH is widely used but possesses unique traits like rapid growth and poor cyst formation compared to other type I strains.
• Understanding genetic and host-modulating differences between type I strains is crucial for characterizing Toxoplasma biology.

Purpose of the Study:

• To identify candidate genes responsible for phenotypic variations between Toxoplasma gondii type I strains RH and GT1.
• To investigate differential host cell modulation by type I strains through host transcriptional profiling.

Main Methods:

• Whole genome sequencing to identify single nucleotide polymorphisms (SNPs) and insertions/deletions (indels) between RH and GT1.
• Comparative transcriptomics to analyze differential gene expression in the parasite.
• Host transcriptional profiling to assess host pathway modulation.

Main Results:

• 1,394 SNPs/indels were identified between RH and GT1, alongside differential gene expression.
• A GRA2 polymorphism was linked to differences in interferon gamma response evasion.
• Host transcriptional profiling revealed differential modulation of NF-κB-regulated genes (e.g., IL-12p40) by type I strains, attributed to GRA15 polymorphisms. RH uniquely recruited phosphorylated IκBα to the vacuole membrane, partly dependent on GRA2.

Conclusions:

• Comparative genomics and transcriptomics identified candidate parasite genes (GRA2, GRA15) contributing to phenotypic variation among type I strains.
• Differentially modulated host pathways were identified, providing a basis for future research into type I strain phenotypic differences.