Toxoplasma gondii
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REPOSITORIES: ENA
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Project description:Toxoplasma gondii is a parasitic protist that is the agent of toxoplasmosis. It is capable of infecting all mammals, 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. T. gondii contains two organelles of endosymbiotic origin: the mitochondrion and the apicoplast, which is a non-photosynthetic plastid. These organelles contain important biochemical pathways which might be interesting targets for future therapeutic strategies. Iron-sulfur clusters are one of the most ancient and ubiquitous prosthetic groups, and they are required by a variety of proteins involved in important metabolic processes. As for plants, T. gondii has several pathways for biosynthesis of iron-sulfur proteins, located in three different cellular compartments: the cytoplasm, the mitochondrion and the apicoplast. We have investigated the relative contributions of the mitochondrion and the apicoplast to the iron-sulfur proteome of the parasite by generating specific mutants for key proteins of the mitochondrial (TgIscU) and plastidic (TgSufS) pathways, on which we performed a quantitative proteomic analysis.
2021-11-09 | PXD023854 | Pride
Project description:Lysine lactylation (Kla) is a new posttranslational modification (PTM) identified in histone and nonhistone proteins of several eukaryotic cells that directly activate gene expression and DNA replication. However, very little is known about their scope and cellular distribution in apicomplexan parasites that are important to public and animal health. Toxoplasma gondii, the agent of toxoplasmosis, is one of obligate intracellular apicomplexan parasite that can infect all kinds of nucleated cells of animals and humans. Using this parasite as model organism, herein, we produced the first global lysine lactylome profile through LC-MS/MS. Overall, a total of 983 Kla sites occurred on 523 lactylated proteins were identified in Toxoplasma tachyzoites, the acute toxoplasmosis-causing stage. Bioinformatics analysis revealed that these lactylated proteins are evolutionarily conserved and involved in a wide variety of cellular functions such as energy metabolism, gene regulation and protein biosynthesis. Moreover, the results from subcellular localization analysis and IFA showed that the majority of lactylated T. gondii proteins localized in the nucleus, indicating a potential impact of Kla on gene regulation. Notably, an extensive batch of parasite-specific proteins unique to Apicomplexa is lactylated in T. gondii. Our findings revealed that Kla was widespread in the early branching eukaryotic cell, and that lactylated proteins, including a crowd of unique parasite proteins, were involved in a remarkably diverse array of cellular functions. These valuable data will improve our understanding of the evolution of Kla while potentially providing novel therapeutic avenues.
2022-06-09 | PXD031526 | 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: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: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:Apicomplexan parasites cause numerous diseases in humans and animals, including malaria (Plasmodium species) and toxoplasmosis (Toxoplasma gondii). Despite being a major drug target, the protein composition of the coenzyme Q:cytochrome c oxidoreductase complex (Complex III) in these parasites was previously unknown. Our work highlights the divergence of mitochondrial ETC Complex III composition in apicomplexan parasites and provides a broader understanding of Complex III evolution. Our study also provides important insights into what sets this major drug target apart from the equivalent complex in host species. Future studies can build on our findings to reveal how novel subunits contribute to Complex III function to further investigate this important drug target.
2021-01-27 | PXD018781 | Pride
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.
2021-08-18 | PXD028016 | iProX
Project description:Toxoplasma gondii is an obligate intracellular protozoan parasite that poses a severe threat to human health, especially those immune-compromised individuals. Sulfadiazine sodium (SDZ) is widely used for the treatment of human toxoplasmosis. However, systems biology researches on the therapeutic effects and mechanisms are not yet well performed. After T. gondii GT1 (Genotype I) infection, BALB/c mice were treated orally with SDZ (250 µg/mL in water) for consecutive 12 days. Mice showed typical acute toxoplasmosis symptoms on day 20 post infection, and 20 percent survived on day 30 post infection and established a chronic infection. An untargeted metabolomics approach based on an UPLC-MS/MS method was employed to identify the serum metabolic changes during SDZ treatment. Multivariate statistical analyses (PCA and PLS-DA) were employed to profile the serum metabolomes from the control mice, acute infection mice and SDZ treated mice. In total, 16,426 metabolite ions could be detected and 14,039 of them were consistently detected in more than 70% of the runs. Our results identified common and uniquely perturbed metabolites and pathways among acutely infected or SDZ treated groups. Acutely infected mice showed a dramatic global metabolic perturbations, and SDZ had a favorable therapeutic effect on parasite-induced acute toxoplasmosis by adjusting the metabolic disorders. Notably, serum metabolomics is proved to be a powerful and reliable approach into the surveillance of disease progression and treatment. More importantly, findings in this study will help provide useful data support for the development of new and safe pharmaceuticals against human toxoplasmosis.
2019-06-18 | MTBLS852 | MetaboLights