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Genetic basis for phenotypic differences between different Toxoplasma gondii type I strains.
- Source :
-
BMC genomics [BMC Genomics] 2013 Jul 10; Vol. 14, pp. 467. Date of Electronic Publication: 2013 Jul 10. - Publication Year :
- 2013
-
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.<br />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-ĸB, such as interleukin (IL)-12p40, were differentially modulated by the different type I strains. We subsequently showed that this difference in NF-ĸB activation was due to polymorphisms in GRA15. Furthermore, we observed that RH, but not other type I strains, recruited phosphorylated IĸBα (a component of the NF-ĸB complex) to the parasitophorous vacuole membrane and this recruitment of p- IĸBα was partially dependent on GRA2.<br />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.
- Subjects :
- Animals
Fibroblasts parasitology
Gene Expression Regulation
Genes, Protozoan genetics
HEK293 Cells
Humans
Interleukin-12 Subunit p40 metabolism
Intracellular Membranes metabolism
Intracellular Membranes parasitology
Macrophages metabolism
Macrophages parasitology
Mice
NF-kappa B metabolism
Polymorphism, Single Nucleotide
Protein Transport
Protozoan Proteins genetics
Protozoan Proteins metabolism
Species Specificity
Toxoplasma metabolism
Vacuoles metabolism
Phenotype
Toxoplasma genetics
Toxoplasma physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1471-2164
- Volume :
- 14
- Database :
- MEDLINE
- Journal :
- BMC genomics
- Publication Type :
- Academic Journal
- Accession number :
- 23837824
- Full Text :
- https://doi.org/10.1186/1471-2164-14-467