Theileria Epigenetics
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ABSTRACT:
PROVIDER: PRJEB33792 | ENA |
REPOSITORIES: ENA
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Project description:Intracellular pathogens develop elaborate mechanisms to survive within the hostile environments of host cells. Theileria parasites infect bovine leukocytes and cause devastating diseases in cattle in developing countries. Theileria spp. have evolved sophisticated strategies to hijack host leukocytes, inducing proliferative and invasive phenotypes characteristic of cell transformation. Intracellular Theileria parasites secrete proteins into the host cell and recruit host proteins to induce oncogenic signaling for parasite survival. It is unknown how Theileria parasites evade host cell defense mechanisms, such as autophagy, to survive within host cells. Here, we show that Theileria annulata parasites sequester the host eIF5A protein to their surface to escape elimination by autophagic processes. We identified a small-molecule compound that reduces parasite load by inducing autophagic flux in host leukocytes, thereby uncoupling Theileria parasite survival from host cell survival. We took a chemical genetics approach to show that this compound induced host autophagy mechanisms and the formation of autophagic structures via AMPK activation and the release of the host protein eIF5A which is sequestered at the parasite surface. The sequestration of host eIF5A to the parasite surface offers a strategy to escape elimination by autophagic mechanisms. These results show how intracellular pathogens can avoid host defense mechanisms and identify a new anti-Theileria drug that induces autophagy to target parasite removal.
2023-12-19 | GSE250088 | GEO
Project description:We report significant changes in six bovine miRNA in vesicles from Theileria annulata infected cells
2019-05-14 | GSE118456 | GEO
Project description:Intracellular pathogens develop elaborate mechanisms to survive within the hostile environments of host cells. Theileria parasites infect bovine leukocytes and cause devastating diseases in cattle in developing countries. Theileria spp. have evolved sophisticated strategies to hijack host leukocytes, inducing proliferative and invasive phenotypes characteristic of cell transformation. Intracellular Theileria parasites secrete proteins into the host cell and recruit host proteins to induce oncogenic signaling for parasite survival. It is unknown how Theileria parasites evade host cell defense mechanisms, such as autophagy, to survive within host cells. Here, we show that Theileria annulata parasites sequester the host eIF5a protein to their surface to escape elimination by autophagic processes. We identified a small-molecule compound that reduces parasite load by inducing autophagic flux in host leukocytes, thereby uncoupling Theileria parasite survival from host cell survival. We took a chemical genetics approach to show that this compound induced host autophagy mechanisms and the formation of autophagic structures via AMPK activation and the release of the host protein eIF5A which is sequestered at the parasite surface. The sequestration of host eIF5a to the parasite surface offers a strategy to escape elimination by autophagic mechanisms. These results show how intracellular pathogens can avoid host defense mechanisms and identify a new anti-Theileria drug that induces autophagy to target parasite removal.
2024-05-24 | PXD047937 | Pride
Project description:Comparision of Theileria annulata and Theileria parva genomes
| PRJNA14000 | ENA
Project description:The experiment investigates bovine gene expression in response to LPS in uninfected and Theileria annulata-infected cell cultures A subset of genes are identified which are activated in response to LPS stimulation with further modulation due to parasite infection.
2012-10-01 | GSE36428 | GEO
Project description:Investigation of parasite (T. annulata) gene expression over the course of the life-cycle (sporozoite->macroschizont->merozoite->piroplasm). The study focused on the expression of known and putative transcription factors, in particular members of the ApiAP2 gene family. Up-stream motifs associated with stage-specifically expressed genes were identified during the course of the analysis. The experiment investigates Theileria annulata gene expression over a differentiation time-course - sporozoite through to piroplasm. 20 samples were analyzed - 4 x sporozoite (replicates), 3 x macroschizont (replicates), 3 x day 4, 3 x day 7, 3 x day 9 (replicates) and 4 x piroplasm (replicates)
2015-07-28 | E-GEOD-71307 | biostudies-arrayexpress
Project description:Theileria annulata is a tick-transmitted apicomplexan parasite that infects and transforms bovine leukocytes into disseminating tumors that cause a disease called tropical theileriosis. Using comparative transcriptomics we identified genes transcriptionally perturbed during Theileria-induced transformation and highlighted a small set of genes associated with leukocyte dissemination. CRISPR/Cas9-mediated knock-down of GZMA and RASGRP1 in macrophages attenuated for dissemination led to a regain in their dissemination in Rag2/gC mice confirming their suppressor roles in vivo. Comparing the transcriptomes of 934 human cancer cell lines to that of Theileria-transformed bovine B cells again highlighted GZMA and RASGRP1 and CRISPR-mediated overexpression of GZMA and RASGRP1 dampened the dissemination potential of human B-lymphomas. The ensemble provide evidence for a novel suppressor function in the dissemination of both T. annulata-transformed bovine leukocytes and human B-lymphomas.
2020-08-18 | GSE135377 | GEO
Project description:Theileria annulata histone deacetylase 1 (TaHDAC1) regulates schizont to merozoite stage conversion
| PRJEB50801 | ENA
Project description:The experiment investigates bovine gene expression in response to LPS in uninfected and Theileria annulata-infected cell cultures A subset of genes are identified which are activated in response to LPS stimulation with further modulation due to parasite infection. Six experimental conditions with three replicates per condition. Total RNA prepared from cell cultures. BL20 (uninfected bovine lymphosarcoma cell line), BL20 4 hours post-LPS stimulation, BL20 18 hours post-LPS, TBL (T. annulata infected bovine cell line), TBL 4 hours post-LPS, TBL 18 hours post-LPS. Each hydridisation represents bovine and parasite gene expression on a single channel and 2 technical replicates of each probeset are represented on the chip.
2012-10-01 | E-GEOD-36428 | biostudies-arrayexpress
Project description:The experiment investigates bovine gene expression in response to BW720c treatment in uninfected and Theileria annulata-infected cell cultures Theileria annulata, an intracellular parasite of bovine lymphoid cells, induces substantial phenotypic alterations to its host cell including continuous proliferation, cytoskeletal changes and resistance to apoptosis. While parasite induced modulation of host cell signal transduction pathways and NFκB activation are established, there remains considerable speculation on the complexities of the parasite directed control mechanisms that govern these radical changes to the host cell. Our objectives in this study were to provide a comprehensive analysis of the global changes to host cell gene expression with emphasis on those that result from direct intervention by the parasite. By using comparative microarray analysis of an uninfected bovine cell line and its Theileria infected counterpart, in conjunction with use of the specific parasitacidal agent, buparvaquone, we have identified a large number of host cell gene expression changes that result from parasite infection. Our results indicate that the viable parasite can irreversibly modify the transformed phenotype of a bovine cell line. 50% of genes with altered expression failed to show a reversible response to parasite death, a possible contributing factor to initiation of host cell apoptosis. The genes that did show an early predicted response to loss of parasite viability highlighted a sub-group of genes that are likely to be under direct control by parasite infection. Network and pathway analysis demonstrated that this sub-group is significantly enriched for genes involved in regulation of expression and chromatin modification. The results provide evidence that the Theileria parasite has the regulatory capacity to generate widespread change to host cell gene expression in a complex and reversible manner. Six experimental conditions with three replicates per condition. Total RNA prepared from cell cultures. BL20 (uninfected bovine lymphosarcoma cell line), BL20 24 hours post-BW720c treatment, BL20 48 hours post-BW720c, TBL (T. annulata infected bovine cell line), TBL 24 hours post-BW720c, TBL 48 hours post-BW720c. Each hydridisation represents bovine and parasite gene expression on a single channel and 2 technical replicates of each probeset are represented on the chip.
2013-07-04 | E-GEOD-44414 | biostudies-arrayexpress