Toxoplasma gondii
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Project description:Toxoplasma gondii is a parasitic protist that is the agent of toxoplasmosis. It is capable of infecting a wide variety of vertebrates, including humans. The infection is mainly asymptomatic in immunocompetent patients, but in case of immunosuppression or for the congenital form of toxoplasmosis it can lead to severe pathologies with a possible fatal outcome. Like for other eukaryotes, many key cellular functions in T. gondii involve proteins containing an iron-sulfur cluster as a cofactor. Cytosolic and nuclear iron-sulfur proteins depend on a specific pathway for assembling their iron-sulfur cofactor. We have investigated the T. gondii homolog of the HCF101 protein, initially characterized in plants as a chloroplast-based iron-sulfur transfer protein, by co-immunoprecipitating associated protein partners and identifying them by mass spectrometry. It confirmed that T. gondii HCF101 is not involved in plastid-based iron-sulfur metabolism, but in the biogenesis of cytosolic and nuclear iron-sulfur proteins instead.
2025-01-24 | PXD051551 | Pride
Project description:Transcriptome analysis of peritoneal lavage of mice infected with T. gondii Toxoplasma gondii is the causative agent of toxoplasmosis in human and animals. In mouse model, T. gondii strains can be divided into three groups, including the virulent, intermediately virulent and non-virulent. The clonal Type I, II and III T. gondii strains belong to these three groups respectively. To better understand the basis of virulence phenotypes, we investigated mouse gene expression responses to the infection of different T. gondii strains at day 5 post intraperitoneal inoculation with 500 tachyzoites. The transcriptomes of mouse peritoneal cells showed that 1927, 1573, and 1009 transcripts were altered more than 2 fold by Type I, II and III infections, respectively, and majority of altered transcripts were shared. Overall transcription patterns were similar in Type I and Type II infections and both had greater changes than that of Type III. Quantification of parasite burden in mouse spleens showed that Type I was 1000 times higher than Type II, and Type II was 20 times higher than Type III. Fluorescence activated cell sorting revealed that Type I and II infections had comparable macrophage populations and both were higher than Type III infection. In addition, Type I infection had higher percentage of neutrophils than that of Type II and III. Taken together, these results suggested that there is a common gene expression response to T. gondii infection in mice. This response is further modified by parasite strain specific factors that determine their distinct virulence phenotypes. We analyzed mRNA from female CD1 outbred mice, 6-8 weeks old infected with Type I, II and III T. gondii strains. We used the Affymetrix Mouse Gene 1.0 ST platform. Raw array data was processed by Partek® Genomics SuiteTM software. Three replicates were performed for Type I-GT1 and Type III-CTG and two replicates for Type II- PTG.
2011-12-22 | E-GEOD-34416 | biostudies-arrayexpress
Project description:Toxoplasma gondii and Cryptosporidium species are apicomplexan parasites of significant medical and veterinary importance. Although current therapeutic options for toxoplasmosis and cryptosporidiosis demonstrate notable efficacy, their clinical efficacy is often limited by suboptimal efficacy and frequent adverse effects. Moreover, therapeutic alternatives remain limited or nonexistent, particularly for cryptosporidiosis, for which nitazoxanide is currently the only approved medication to treat diarrhea in adults and children older than 1 year of age. To identify alternative therapeutic options for addressing these health challenges, we performe a phenotypic screening of an FDA-approved drug repurposing library against Toxoplasma. This screening identifies LY2090314 as a potent inhibitor of T. gondii and Cryptosporidium growth in mammalian cells. Through a target deconvolution strategy combining forward genetics, transcriptome sequencing, and computational mutation analysis, we elucidate the parasiticidal mechanism of LY2090314 and demonstrate that TgGSK3 kinase is its primary molecular target. We also report the first X-ray crystal structure of LY2090314 bound to TgGSK3, resolved at 2.1 Å, which reveals an interaction mode characteristic of type I ATP-competitive inhibitors. Furthermore, interactome analysis uncovers functional connections between TgGSK3 and key cytoskeletal and signaling regulators, providing insights into compound’s effects. Collectively, these findings validate TgGSK3 as a promising therapeutic target for toxoplasmosis and offer mechanistic insights into apicomplexan GSK3 biology.
2025-01-20 | GSE286338 | GEO
Project description:Toxoplasma gondii is a parasitic protist that is the agent of toxoplasmosis. It is capable of infecting a wide variety of vertebrates, including humans. The infection is mainly asymptomatic in immunocompetent patients, but in case of immunosuppression or for the congenital form of toxoplasmosis it can lead to severe pathologies with a possible fatal outcome. Like for other eukaryotes, many key cellular functions in T. gondii involve proteins containing an iron-sulfur cluster as a cofactor. Cytosolic and nuclear iron-sulfur proteins depend on a specific pathway for assembling their iron-sulfur cofactor. We have investigated the T. gondii homolog of the HCF101 protein, initially characterized in plants as a chloroplast-based iron-sulfur transfer protein, by generating a specific mutant on which we performed a quantitative proteomic analysis to get insights into its function in the parasites. We discovered that T. gondii HCF101 is not involved in plastid-based iron-sulfur metabolism, but in the biogenesis of cytosolic and nuclear iron-sulfur proteins instead. Control TATi ΔKu80 dataset is similar to the one provided in PRIDE entry PXD048386
2025-01-24 | PXD051549 | Pride
Project description:Transcriptome analysis of peritoneal lavage of mice infected with T. gondii Toxoplasma gondii is the causative agent of toxoplasmosis in human and animals. In mouse model, T. gondii strains can be divided into three groups, including the virulent, intermediately virulent and non-virulent. The clonal Type I, II and III T. gondii strains belong to these three groups respectively. To better understand the basis of virulence phenotypes, we investigated mouse gene expression responses to the infection of different T. gondii strains at day 5 post intraperitoneal inoculation with 500 tachyzoites. The transcriptomes of mouse peritoneal cells showed that 1927, 1573, and 1009 transcripts were altered more than 2 fold by Type I, II and III infections, respectively, and majority of altered transcripts were shared. Overall transcription patterns were similar in Type I and Type II infections and both had greater changes than that of Type III. Quantification of parasite burden in mouse spleens showed that Type I was 1000 times higher than Type II, and Type II was 20 times higher than Type III. Fluorescence activated cell sorting revealed that Type I and II infections had comparable macrophage populations and both were higher than Type III infection. In addition, Type I infection had higher percentage of neutrophils than that of Type II and III. Taken together, these results suggested that there is a common gene expression response to T. gondii infection in mice. This response is further modified by parasite strain specific factors that determine their distinct virulence phenotypes.
2011-12-22 | GSE34416 | GEO
Project description:Toxoplasma gondii is a parasitic protist that is the agent of toxoplasmosis. It is capable of infecting a wide variety of vertebrates, including humans. The infection is mainly asymptomatic in immunocompetent patients, but in case of immunosuppression or for the congenital form of toxoplasmosis it can lead to severe pathologies with a possible fatal outcome. Like for other eukaryotes, many key cellular functions in T. gondii involve proteins containing an iron-sulfur cluster as a cofactor. Cytosolic and nuclear iron-sulfur proteins depend on a specific pathway for assembling their iron-sulfur cofactor. It was demonstrated in other eukaryotes (ie in the budding yeast model) that a sulfur-containing precursor originating from the mitochondrion and transported through the ABCB7 transporter is essential for building cytosolic iron-sulfur clusters. We have investigated the T. gondii homolog of the ABCB7 transporter by generating a specific mutant on which we performed a quantitative proteomic analysis to get insights into its involvement in the biogenesis of cytosolic and nuclear iron-sulfur proteins.
2024-08-09 | PXD048386 | Pride
Project description:Toxoplasmosis is a major health issue worldwide especially for immune-deficient individuals and the offspring of newly infected mothers. It is caused by a unicellular intracellular parasite called Toxoplasma gondii. Although the drugs commonly used to treat toxoplasmosis are efficient, they present serious side effects and adverse events are common. Therefore, there is a need for the discovery of new compounds with potent anti-T. gondii activity. We have tested compounds designed to target enzymes that are involved in the epigenetic regulation of gene expression. Among the most active compounds, we identified a HDAC inhibitor that shows an IC50 of around 30 nM with a selectivity index of more than 100. MC1742 is active at inhibiting the growth of the parasite in vitro but also at preventing the consequences of the acute disease in vivo. This compound induces a hyper-acetylation of histones while acetylated tubulin level remains unchanged. After MC1742 treatment, the parasite expression profile is profoundly changed with the activation of genes preferentially expressed in the sexual stages that are normally repressed at the tachyzoite stage. These findings suggest that this compound disturbs the T. gondii gene expression program, inducing parasite death.
2024-05-22 | GSE175919 | GEO
Project description:Serological diagnostic methods (anti-T. gondii IgM and IgG) and PCR-based diagnosis are the two main methods used to diagnose acute toxoplasmosis. However, serological assays pose limitations, such as IgM false positives, the long-lasting presence of residual specific Abs, and potential IgG immaturity, complicating diagnostic decision making. Moreover, PCR-based diagnosis is not always useful in the case of acute acquired toxoplasmosis. T. gondii excretory-secretory Ags (ESAs) form the majority of the circulating Ags (CAgs) present in serum of patients with acute toxoplasmosis and have been proven to be useful and valuable for acute toxoplasmosis diagnosis. Additionally, the infection route has no effect on the detection of CAgs. Particularly, they have been shown to exist in the cerebrospinal fluid of HIV-infected patients with cerebral toxoplasmosis. Thus, screening and identification of diagnostic markers from CAg components can therefore help to improve the accuracy of acute toxoplasmosis diagnosis.
| PXD028016 |