BMC Genomics. 2013 Jul 10;14(1):467. [Epub ahead of print]

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

Yang N, Farrell A, Niedelman W, Melo M, Lu D, Julien L, Marth GT, Gubbels MJ, Saeij JP.

Abstract

BACKGROUND:

Toxoplasma gondii has a largely clonal population in North America and Europe, with types I, II and III clonal lineages accounting for the majority of strains isolated from patients. RH, a particular type I strain, is most frequently used to characterize Toxoplasma biology. However, compared to other type I strains, RH has unique characteristics such as faster growth, increased extracellular survival rate and inability to form orally infectious cysts. Thus, to identify candidate genes that could account for these parasite phenotypic differences, we determined genetic differences and differential parasite gene expression between RH and another type I strain, GT1. Moreover, as differences in host cell modulation could affect Toxoplasma replication in the host, we determined differentially modulated host processes among the type I strains through host transcriptional profiling.

RESULTS:

Through whole genome sequencing, we identified 1,394 single nucleotide polymorphisms (SNPs) and insertions/deletions (indels) between RH and GT1. These SNPs/indels together with parasite gene expression differences between RH and GT1 were used to identify candidate genes that could account for type I phenotypic differences. A polymorphism in dense granule protein, GRA2, determined RH and GT1 differences in the evasion of the interferon gamma response. In addition, host transcriptional profiling identified that genes regulated by NF-[latin small letter kra]B, such as interleukin (IL)-12p40, were differentially modulated by the different type I strains. We subsequently showed that this difference in NF-[latin small letter kra]B activation was due to polymorphisms in GRA15. Furthermore, we observed that RH, but not other type I strains, recruited phosphorylated I[latin small letter kra]Balpha (a component of the NF-[latin small letter kra]B complex) to the parasitophorous vacuole membrane and this recruitment of p- I[latin small letter kra]Balpha was partially dependent on GRA2.

CONCLUSIONS:

We identified candidate parasite genes that could be responsible for phenotypic variation among the type I strains through comparative genomics and transcriptomics. We also identified differentially modulated host pathways among the type I strains, and these can serve as a guideline for future studies in examining the phenotypic differences among type I strains.

PMID:

 

23837824

 

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