Anti-Toxoplasma effect of Panobinostat
Ontology highlight
ABSTRACT:
ORGANISM(S): Toxoplasma Gondii Rh-88
SUBMITTER: 
Chunxue Zhou
PROVIDER: PXD078834 | iProX | Tue May 26 00:00:00 GMT+01:00 2026
REPOSITORIES: iProX
Similar Datasets
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:Toxoplasma gondii has numerous, large, paralogous gene families that are likely critical for supporting its unparalleled host range: nearly any nucleated cell in almost any warm-blooded animal. The SRS (SAG1-related sequence) gene family encodes over 100 proteins, the most abundant of which are thought to be involved in parasite attachment and, based on their stage-specific expression, evading the host immune response. For most SRS proteins, however, little is understood about their function and expression profile. Single-parasite RNA-sequencing previously demonstrated that across an entire population of lab-grown tachyzoites, transcripts for over 70 SRS genes were detected in at least one parasite. In any one parasite, however, transcripts for an average of only 7 SRS genes were detected, two of which, SAG1 and SAG2A, were extremely abundant and detected in virtually all. These data do not address whether this pattern of sporadic SRS gene expression is consistently inherited among the progeny of a given parasite or arises independently of lineage. We hypothesized that if SRS expression signatures are stably inherited by progeny, subclones isolated from a cloned parent would be more alike in their expression signatures than they are to the offspring of another clone. In this report, we compare transcriptomes of clonally derived parasites to determine the degree to which expression of the SRS family is stably inherited in individual parasites. Our data indicate that in RH tachyzoites, SRS genes are variably expressed even between parasite samples subcloned from the same parent within approximately 10 parasite divisions (72 hours). This suggests that the pattern of sporadically expressed SRS genes is highly variable and not driven by inheritance mechanisms, at least under our conditions.
2021-12-20 | GSE191153 | GEO
Project description:The Toxoplasma gondii G1 RESTRICTION checkpoint operates the switch between parasite growth and differentiation. The Cdk-related G1 kinase TgCrk2 forms alternative complexes with atypical cyclins (TgCycP1, TgCycP2 and TgCyc5) in the rapidly dividing developmentally incompetent RH and slower dividing developmentally competent ME49 tachyzoites and bradyzoites. The TgCycP1 expression interferes with bradyzoite differentiation. The TgCycP2 regulates G1 in the developmentally competent ME49 but not in the developmentally incompetent RH tachyzoites. Examination of TgCycP2 and TgCyc5 in alkaline induced and spontaneous bradyzoite differentiation (rat embryonic brain cells) models confirmed TgCycP2 role in bradyzoite replication and revealed that stress induced TgCyc5 is critical for efficient tissue cyst maturation.
2022-04-23 | GSE200962 | GEO
Project description:In order to better understand how the coccidiocide monensin affects T. gondii, we analyzed the effect of monensin on gene expression of intracellular parasites through microarrays. We compared RNA collected either from RH strain tachyzoites 24 hrs after invasion of human foreskin fibroblasts, or 24 hrs after invasion followed by 24 hrs exposure to 2.5ng monensin/ml in tissue culture medium.
2010-11-06 | E-GEOD-25177 | biostudies-arrayexpress
Project description:Toxoplasma gondii is a protozoan parasite that causes persistent infection in warm-blooded vertebrates by undergoing differentiation from a replicative stage (tachyzoites) to a latent encysted stage (bradyzoites). Stage differentiation is critical for transmission and pathogenesis and relies on gene regulation driven by a network of transcription and epigenetic factors. We previously found in non-cystogenic type I RH strain parasites that the lysine acetyltransferase (KAT), GCN5a, is dispensable in tachyzoites but required to upregulate stress-response genes, suggesting a link with bradyzoite conversion. To address this possibility, we generated endogenously tagged GCN5a parasites and a genetic knockout in cystogenic type II Pru strain. We show that GCN5a protein, but not mRNA, increases during differentiation and complexes with unique protein partners, most of which contain AP2 domains. Pru strain tachyzoites lacking GCN5a augment bradyzoite-specific gene expression in the absence of stress. Loss of GCN5a slowed tachyzoite replication and heightened sensitivity to bradyzoite conversion but resulted in smaller cyst sizes compared to wildtype. Using CUT&Tag, we delineated the chromosomal occupancy of GCN5a relative to the essential KAT, GCN5b. While GCN5b localizes to coding regions, GCN5a surprisingly localizes exclusively to telomeres. These findings suggest that the loss of GCN5a leads to telomere dysfunction, which slows replication and promotes the transition to latency.
2025-02-04 | GSE286090 | GEO
Project description:Toxoplasma gondii is a protozoan parasite that causes persistent infection in warm-blooded vertebrates by undergoing differentiation from a replicative stage (tachyzoites) to a latent encysted stage (bradyzoites). Stage differentiation is critical for transmission and pathogenesis and relies on gene regulation driven by a network of transcription and epigenetic factors. We previously found in non-cystogenic type I RH strain parasites that the lysine acetyltransferase (KAT), GCN5a, is dispensable in tachyzoites but required to upregulate stress-response genes, suggesting a link with bradyzoite conversion. To address this possibility, we generated endogenously tagged GCN5a parasites and a genetic knockout in cystogenic type II Pru strain. We show that GCN5a protein, but not mRNA, increases during differentiation and complexes with unique protein partners, most of which contain AP2 domains. Pru strain tachyzoites lacking GCN5a augment bradyzoite-specific gene expression in the absence of stress. Loss of GCN5a slowed tachyzoite replication and heightened sensitivity to bradyzoite conversion but resulted in smaller cyst sizes compared to wildtype. Using CUT&Tag, we delineated the chromosomal occupancy of GCN5a relative to the essential KAT, GCN5b. While GCN5b localizes to coding regions, GCN5a surprisingly localizes exclusively to telomeres. These findings suggest that the loss of GCN5a leads to telomere dysfunction, which slows replication and promotes the transition to latency.
2025-02-04 | GSE286088 | GEO
Project description:Toxoplasma gondii pathogenesis includes the invasion of host cells by extracellular parasites (tachyzoites), replication of intracellular tachyzoites, and differentiation to a latent bradyzoite stage. Whole genome expression profiling was carried out using the newly developed Affymetrix ToxoGeneChip (GeneChip Tgondiia520372) in order to analyze the ~8,000 predicted genes in the T. gondii genome of mutants and wild-type, allowing for full-scale expression profiling during bradyzoite differentiation in vitro. RNA from mutant and wild-type parasites was extracted and hybridized to the ToxoGeneChip. We harvested extracellular tachyzoites from freshly lysed fibroblasts (ET, 0h), intracellular tachyzoites (IT, 24h post-invasion) and parasites subjected to bradyzoite growth conditions for 72h (B72, 72h of induction). Extracellular parasites from freshly lysed fibroblasts were harvested for the seven mutant parasite lines (12K, 13P, B7, 11P, 11K, 7K and P11) and mutant parasites subjected to bradyzoite differentiation conditions for 72h. For a few samples we also harvested parasites 11h post egress of host cells. A time course was carried out with wild-type: parasites subjected to bradyzoite growth conditions for 24h, 36h and 48h.
2010-07-27 | E-GEOD-23174 | biostudies-arrayexpress
Project description:Although apicomplexans lack conventional R-point regulators, presence of the quiescent G1 forms of 43 parasites, including mature T. gondii bradyzoites suggests that a functional RESTRICTION checkpoint 44 exists in apicomplexan parasites. We showed that Cdk-related G1 kinase TgCrk2 forms alternative 45 complexes with atypical cyclins (TgCycP1, TgCycP2 and TgCyc5) in the rapidly dividing developmentally 46 incompetent RH and slower dividing developmentally competent ME49 tachyzoites and bradyzoites. 47 Examination of individual cyclins verified the correlation of cyclin expression with growth dependence and 48 development capacity of type I RH and type II ME49 strains. We demonstrated that rapidly dividing RH 49 tachyzoites are dependent on TgCycP1 and expression of TgCycP1 interferes with bradyzoite 50 differentiation. By using an auxin-induced degradation (AID) model, we established that TgCycP2 51 regulates G1 duration in the developmentally competent ME49 tachyzoites but not in the developmentally 52 incompetent RH tachyzoites. We also tested the functions of TgCycP2 and TgCyc5 in alkaline induced in 53 vitro model and in ex vivo model of spontaneous bradyzoite differentiation (rat embryonic brain cells). 54 Based on functional and global gene expression analyses, we determined that TgCycP2 also regulates 55 bradyzoite replication, while stress- or host-induced TgCyc5 was critical for efficient bradyzoite conversion 56 and tissue cyst maturation.
2022-08-12 | PXD033109 | Pride
Project description:The normally virulent type-I RH parasite is rendered avirulent when lacking ROP5. The avirulent phenotype is a consequence of interaction with the host innate immune system. We sought to understand if ROP5 alters host gene expression in order to escape host defenses. We saw no gene expression differences between host cells infected with wt (RH∆ku80) or RH∆ku80∆rop5 parasites. We have included uninfected HFF samples that were harvested in parallel with the infected samples.
2012-09-13 | GSE32104 | GEO
Project description:Differential gene expression analysis of TgAP2IV-4 knockout parasites in type I RH diCRE (RHCre) and type II Prudku80 (PruQ) genetic background The gene regulatory role for TgAP2IV-4 was evaluated, in vitro, as tachyzoites (pH 7.0) in 8 strains: RHCre-AP2IV-4 floxed; RHCre-delta_ap2IV-4 clones 27 and 30, PSMB794 cosmid complemented RHCre-dAP2IV-4 populations; PruQ-AP2IV-4 floxed; PruQ-delta_ap2IV-4 clones 10 and 34.
2017-01-18 | GSE93531 | GEO