Toxoplasma gondii
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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: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: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: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
Project description:Toxoplasma gondii is a globally distributed obligate intracellular parasite which can cause zoonotic toxoplasmosis with great harms. The average death time of mice that infected with Toxoplasma gondii RH strain tachyzoites recovered from the liquid nitrogen was shortened after multiple generations. It has been reported that the parasite is in a state of static virulence during cryopreservation and the virulence of the protozoan parasite can be enhanced after continuous passages in hosts under laboratory conditions. However, no research has been conducted to elucidate its biological mechanism. Herein, we sequenced the T. gondii transcriptome using RNA-Seq technology and performed de novo assembly to investigated the virulence factors expression changes by comparing gene expression profiles between incipiently recovered and completely resuscitated tachyzoites. Transcriptome analysis identified 1,951 differentially expressed transcripts in infected liver, of which 1,752 were significantly downregulated and 199 upregulated. We identified many differentially expressed proteins and genes, including serine/threonine kinase, calnexin, myosin and microtubule-associated protein which have previously been reported to be either involved in cell adhesion, parasite gliding or participate in cell invasion. The great majority of the virulence factors including microneme proteins, rhoptry proteins and dense granule proteins were upregulated in fully recovered tachyzoites. The enhanced virulence of recovered Toxoplasma gondii RH strain from the liquid nitrogen is associated with the up-regulated expression of MICs, ROPs and GRAs. Our data will facilitate future genomic research and in-depth annotation of Toxoplasma gondii RH strain genomes. This study provides a profile of the candidate genes that are suspected to be involved with virulence enhancement of recovered Toxoplasma gondii RH strain tachyzoites. Many further studies should be carried out to confirm the function of the candidate genes. Moreover, the preliminary identification of genes and pathways exhibiting differential expression in complete resuscitation stage may further our general understanding of virulence enhancement in this parasite.
2021-05-14 | GSE114386 | GEO
Project description:Toxoplasmosis is a zoonotic disease caused by a ubiquitous protozoan parasite called Toxoplasma gondii, which can
infect all mammal and bird species throughout the world. seroprevalence varies widely between countries. Studies
have estimated that between 7-34% of people in the UK have been infected with T. gondii. The vast majority of these
people will not have noticed any symptoms, however about 10% of people develop a mild to moderate self limiting
flu-like illness. Following the acute active stage of the infection the parasite persists in the body in the form of cysts,
particularly in heart and skeletal muscle and nervous system tissues, for many years, and usually for life. In
immunocompetent persons these cysts do not pose a health risk. We will use RNA-seq to quantify the transcriptional
response of macrophages to T gondii infection.
This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/
| EGAS00001001708 | EGA