The transcriptome of Toxoplasma gondii

Radke, Jay R.; Behnke, Michael S.; Mackey, Aaron J.; Radke, Josh B.; Roos, David S.; White, Michael

doi:10.1186/1741-7007-3-26

Cited by 158 publications

(85 citation statements)

References 84 publications

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“…The expression patterns of "bradyzoite" genes in H. hammondi sporulated oocysts may be a reflection of their place on the developmental spectrum between tachyzoite and bradyzoite. This spectrum has been described previously for T. gondii strains that differ in their growth characteristics in vitro (e.g., VEG compared to RH [64]) but has yet to be described in multispecies comparisons like those outlined in the present study.…”

Section: Discussionmentioning

confidence: 77%

Hammondia hammondi Harbors Functional Orthologs of the Host-Modulating Effectors GRA15 and ROP16 but Is Distinguished from Toxoplasma gondii by a Unique Transcriptional Profile

et al. 2014

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Toxoplasma gondii and its nearest extant relative, Hammondia hammondi, are phenotypically distinct despite their remarkable similarity in gene content, synteny, and functionality. To begin to identify genetic differences that might drive distinct infection phenotypes of T. gondii and H. hammondi, in the present study we (i) determined whether two known host-interacting proteins, dense granule protein 15 (GRA15) and rhoptry protein 16 (ROP16), were functionally conserved in H. hammondi and (ii) performed the first comparative transcriptional analysis of H. hammondi and T. gondii sporulated oocysts. We found that GRA15 and ROP16 from H. hammondi (HhGRA15 and HhROP16) modulate the host NF-B and STAT6 pathways, respectively, when expressed heterologously in T. gondii. We also found the transcriptomes of H. hammondi and T. gondii to be highly distinct. Consistent with the spontaneous conversion of H. hammondi tachyzoites into bradyzoites both in vitro and in vivo, H. hammondi high-abundance transcripts are enriched for genes that are of greater abundance in T. gondii bradyzoites. We also identified genes that are of high transcript abundance in H. hammondi but are poorly expressed in multiple T. gondii life stages, suggesting that these genes are uniquely expressed in H. hammondi. Taken together, these data confirm the functional conservation of known T. gondii virulence effectors in H. hammondi and point to transcriptional differences as a potential source of the phenotypic differences between these species.

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Section: Discussionmentioning

confidence: 77%

Hammondia hammondi Harbors Functional Orthologs of the Host-Modulating Effectors GRA15 and ROP16 but Is Distinguished from Toxoplasma gondii by a Unique Transcriptional Profile

et al. 2014

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“…This has led to the proposal that gene regulation in apicomplexan parasites is controlled mainly via RNA stability [6], despite the tightly regulated patterns of gene expression observed in different stages of the life cycle of T. gondii [8] and Plasmodium falciparum [9]. However, that certain DNA motifs are recurrent in the promoters of these organisms and bind to nuclear factors [10−14] suggests that unrecognized transcription factors may exist, but are not encoded by genes with recognizable structural features.…”

Section: Introductionmentioning

confidence: 99%

Epigenomic Modifications Predict Active Promoters and Gene Structure in Toxoplasma gondii

et al. 2007

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Mechanisms of gene regulation are poorly understood in Apicomplexa, a phylum that encompasses deadly human pathogens like Plasmodium and Toxoplasma. Initial studies suggest that epigenetic phenomena, including histone modifications and chromatin remodeling, have a profound effect upon gene expression and expression of virulence traits. Using the model organism Toxoplasma gondii, we characterized the epigenetic organization and transcription patterns of a contiguous 1% of the T. gondii genome using custom oligonucleotide microarrays. We show that methylation and acetylation of histones H3 and H4 are landmarks of active promoters in T. gondii that allow us to deduce the position and directionality of gene promoters with >95% accuracy. These histone methylation and acetylation “activation” marks are strongly associated with gene expression. We also demonstrate that the pattern of histone H3 arginine methylation distinguishes certain promoters, illustrating the complexity of the histone modification machinery in Toxoplasma. By integrating epigenetic data, gene prediction analysis, and gene expression data from the tachyzoite stage, we illustrate feasibility of creating an epigenomic map of T. gondii tachyzoite gene expression. Further, we illustrate the utility of the epigenomic map to empirically and biologically annotate the genome and show that this approach enables identification of previously unknown genes. Thus, our epigenomics approach provides novel insights into regulation of gene expression in the Apicomplexa. In addition, with its compact genome, genetic tractability, and discrete life cycle stages, T. gondii provides an important new model to study the evolutionarily conserved components of the histone code.

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“…Tachyzoite-to-bradyzoite conversion seems to be critical for B. besnoiti persistence in the host, and it has been described for other cyst-forming coccidian parasites (Innes, 2007) In cyst-forming coccidian parasites, preliminary comparative studies on the differences between tachyzoite and bradyzoite stages have been carried out by genomic approaches (Cleary et al 2002;Radke et al 2005). Proteomic tools have also been employed to compare different stages in apicomplexan parasites (Florens et al 2002;Lal et al 2009;Marugán-Hernández et al 2010).…”

Section: R E S U L T S a N D Discussionmentioning

confidence: 99%

Identification ofBesnoitia besnoitiproteins that showed differences in abundance between tachyzoite and bradyzoite stages by difference gel electrophoresis

et al. 2013

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Bovine besnoitiosis is a chronic and debilitating disease, caused by the apicomplexan parasite Besnoitia besnoiti. Infection of cattle by B. besnoiti is governed by the tachyzoite stage, which is related to acute infection, and the bradyzoite stage gathered into macroscopic cysts located in subcutaneous tissue in the skin, mucosal membranes and sclera conjunctiva and related to persistence and chronic infection. However, the entire life cycle of this parasite and the molecular mechanisms underlying tachyzoite-to-bradyzoite conversion remain unknown. In this context, a different antigenic pattern has been observed between tachyzoite and bradyzoite extracts. Thus, to identify stage-specific proteins, a difference gel electrophoresis (DIGE) approach was used on tachyzoite and bradyzoite extracts followed by mass spectrometry (MS) analysis. A total of 130 and 132 spots were differentially expressed in bradyzoites and tachyzoites, respectively (average ratio ± 1.5, P<0.05 in t-test). Furthermore, 25 differentially expressed spots were selected and analysed by MALDI-TOF/MS. As a result, 5 up-regulated bradyzoite proteins (GAPDH, ENO1, LDH, SOD and RNA polymerase) and 5 up-regulated tachyzoite proteins (ENO2; LDH; ATP synthase; HSP70 and PDI) were identified. The present results set the basis for the identification of new proteins as drug targets. Moreover, the role of these proteins in tachyzoite-to-bradyzoite conversion and the role of the host cell environment should be a subject of further research.

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The transcriptome of Toxoplasma gondii

Cited by 158 publications

References 84 publications

Hammondia hammondi Harbors Functional Orthologs of the Host-Modulating Effectors GRA15 and ROP16 but Is Distinguished from Toxoplasma gondii by a Unique Transcriptional Profile

Hammondia hammondi Harbors Functional Orthologs of the Host-Modulating Effectors GRA15 and ROP16 but Is Distinguished from Toxoplasma gondii by a Unique Transcriptional Profile

Epigenomic Modifications Predict Active Promoters and Gene Structure in Toxoplasma gondii

Identification ofBesnoitia besnoitiproteins that showed differences in abundance between tachyzoite and bradyzoite stages by difference gel electrophoresis

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