Low Dose Gamma Irradiation of Trypanosoma evansi Parasites Identifies Gene Transcripts Involved in Establishing Disease in Mice Post Irradiation
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ABSTRACT:
ORGANISM(S): Trypanosoma evansi
PROVIDER: GSE202334 | GEO | 2023/05/06
REPOSITORIES: GEO
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Project description:The protozoan parasite Trypanosoma evansi is responsible for causing Surra in a variety of mammalian hosts over a wide geographical area. In order to identify which genes and processes are required to establish disease in mice, parasites were irradiated over a range using a Cobalt60 gamma source. A custom Trypanosome spp. array that covers the genomes of three trypanosome species, T. brucei, T. evansi and T. congolense was designed by Affymetrix with an average of 9300 whole gene transcripts from all three species were targeted. Irradiation differentially affected the abundance of gene transcripts in a dose-dependent trend. We present these genes as necessary for repair from irradiation damage, and essential for disease establishment in mice post irradiation.
2022-05-10 | E-MTAB-11705 | biostudies-arrayexpress
Project description:Trypanosoma vivax is a major pathogen of domestic cattle and wildlife across sub-Saharan Africa. For many years, the WTSI has had a research interest in developing a genome sequence for T. vivax, as part of a wider programme concerning African trypanosome parasites of Humans and animals. In 2012 a draft genome sequence for T. vivax Y486 was published by the WTSI and our collaborators in comparison with related species, T. brucei and T. congolense. This study identified numerous putative genes in T. vivax that have no known affinity and are therefore species-specific. A related transcriptomic study confirmed that some of these putative genes are transcribed, but lacked accuracy and was based on a single parasite life stage only. Until recently, it has not been possible to culture different T. vivax life stages in refined media. There is now the opportunity to use new approaches to produce whole cell RNA for both insect and bloodstream parasite stages. We sequence stage-specific cDNA and identify stage-specific genes, and compare these features with similar data already available for T. brucei and T. congolense, which display substantial differences in their developmental cycles. 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/
2013-03-07 | E-ERAD-100 | biostudies-arrayexpress
Project description:African trypanosomes are dixenous eukaryotic parasites that impose a significant human and veterinary disease burden on sub-Saharan Africa. Diversity between species and life-cycle stages is concomitant with distinct host and tissue tropisms within this group. Here, the spatial proteomes of two African trypanosome species, Trypanosoma brucei and Trypanosoma congolense, have been mapped, each in mammalian and insect life-stages represented by bloodstream form (BSF) and procyclic form (PCF) respectively. Using the hyperLOPIT (hyperplexed localisation of organelle proteins by isotope tagging) methodology, this work has provided four highly comprehensive spatial proteomes.
2023-10-22 | PXD035426 | Pride
Project description:Trypanosomatid parasites undergo developmental regulation to adapt to the different environments encountered during their life cycle. In Trypanosoma brucei, a genome wide selectional screen previously identified a regulator of the protein family ESAG9, which is highly expressed in stumpy forms, a morphologically distinct bloodstream stage adapted for tsetse transmission. This regulator, TbREG9.1, has an orthologue in Trypanosoma congolense, despite the absence of a stumpy morphotype in that parasite species, which is an important cause of livestock trypanosomosis. RNAi mediated gene silencing of TcREG9.1 in Trypanosoma congolense caused a loss of attachment of the parasites to a surface substrate in vitro, a key feature of the biology of these parasites that is distinct from T. brucei. This detachment was phenocopied by treatment of the parasites with a phosphodiesterase inhibitor, which also promotes detachment in the insect trypanosomatid Crithidia fasciculata. RNAseq analysis revealed that TcREG9.1 silencing caused the upregulation of mRNAs for several classes of surface molecules, including transferrin receptor-like molecules, immunodominant proteins, and molecules related to those associated with stumpy development in T. brucei. Depletion of TcREG9.1 in vivo also generated an enhanced level of parasites in the blood circulation consistent with reduced parasite attachment to the microvasculature. The morphological progression to insect forms of the parasite was also perturbed. We propose a model whereby TcREG9.1 acts as a regulator of attachment and development, with detached parasites being adapted for transmission.
2024-02-19 | GSE249623 | GEO
Project description:Purpose: The is a major paucity of knowledge regarding the biology of Trypanosoma congolense, a protozoan parasite primarily responsible for Animal African Trypanosomiasis. In contrast, the closely related species T. brucei, is far better understood. To characterise core metabolism in T. congolense, comparative RNAseq analysis was undertaken to assess similarities and differences in transcript levels of genes associated with metabolism Methods: Samples from both in vitro culture and ex vivo (isolated from murine infections) bloodstream-form T. brucei and T. congolense were RNA-sequenced. Data was analyzed using a pipeline that allows for inter-species comparison Results: T. congolense exhibits increased transcript abundance in genes associated with the glycosomal succinate shunt, as well as mitochondrial metabolism, in particular the catabolism of pyruvate to acetate, compared to T. brucei. These differences occur both in vitro and ex vivo. Furthermore there are differences in nucleotide metabolism, and transcript levels of genes involved in fatty acid synthesis are reduced in T. congolense compared to T. brucei. Conclusions: Comparative RNAseq between two closely related species provided a detailed overview of similarities and differences in core metabolism. This carries significant implications for adaptation to in vitro culture, and drug efficacy, mode of action and mode of resistance.
2021-01-22 | GSE165290 | GEO
Project description:Transmission of Trypanosoma brucei by tsetse flies involves the deposition of the infective quiescent metacyclic stage into the mammalian skin at the site of the fly’s bite. In the skin, the metacyclic parasites reactivate and differentiate into proliferative trypanosomes before colonizing the host's blood and tissues. We have generated an advanced human skin equivalent and used tsetse flies to naturally infect the artificial skin with trypanosomes. We have detailed the chronological order of the parasites' development in the skin and found a rapid activation and differentiation of the tsetse-transmitted cell cycle‑arrested metacyclic trypanosomes to proliferative parasites. Single-parasite transcriptomics documented the biological events during differentiation and host invasion at five different time points. After the establishment of a proliferative trypanosome population in the skin, the parasites entered a reversible quiescence program characterized by slow replication and a strongly reduced metabolism. We termed these quiescent trypanosomes skin tissue forms (STF), which may play an important role in maintaining the trypanosome infection in aparasitemic, asymptomatic individuals.
2021-05-30 | GSE174198 | GEO
Project description:<p>Livestock diseases caused by Trypanosoma congolense, T. vivax and T. brucei, collectively known as nagana, are responsible for billions of dollars in lost food production annually. There is an urgent need for novel therapeutics. Encouragingly, promising antitrypanosomal benzoxaboroles are under veterinary development. Here, we show that the most efficacious subclass of these compounds are prodrugs activated by trypanosome serine carboxypeptidases (CBPs). Drug-resistance to a development candidate, AN11736, emerged readily in T. brucei, due to partial deletion within the locus containing three tandem copies of the CBP genes. T. congolense parasites, which possess a larger array of related CBPs, also developed resistance to AN11736 through deletion within the locus. A genome-scale screen in T. brucei confirmed CBP loss-of-function as the primary mechanism of resistance and CRISPR-Cas9 editing proved that partial deletion within the locus was sufficient to confer resistance. CBP re-expression in either T. brucei or T. congolense AN11736-resistant lines restored drug-susceptibility. CBPs act by cleaving the benzoxaborole AN11736 to a carboxylic acid derivative, revealing a prodrug activation mechanism. Loss of CBP activity results in massive reduction in net uptake of AN11736, indicating that entry is facilitated by the concentration gradient created by prodrug metabolism.</p><p><br></p><p><strong>T. brucei assay</strong> is reported in the current study <a href='https://www.ebi.ac.uk/metabolights/MTBLS1474' rel='noopener noreferrer' target='_blank'><strong>MTBLS1474</strong></a>.</p><p><strong>T. congolense assay</strong> is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS1309' rel='noopener noreferrer' target='_blank'><strong>MTBLS1309</strong></a>.</p><p><br></p><p><strong>Linked cross omic data sets:</strong></p><p>Genome data associated with this study are available in the European Nucleotide Archive (ENA): accession number <a href='https://www.ebi.ac.uk/ena/browser/view/PRJEB34627' rel='noopener noreferrer' target='_blank'>PRJEB34627</a>.</p>
2020-09-23 | MTBLS1474 | MetaboLights
Project description:<p>Livestock diseases caused by Trypanosoma congolense, T. vivax and T. brucei, collectively known as nagana, are responsible for billions of dollars in lost food production annually. There is an urgent need for novel therapeutics. Encouragingly, promising antitrypanosomal benzoxaboroles are under veterinary development. Here, we show that the most efficacious subclass of these compounds are prodrugs activated by trypanosome serine carboxypeptidases (CBPs). Drug-resistance to a development candidate, AN11736, emerged readily in T. brucei, due to partial deletion within the locus containing three tandem copies of the CBP genes. T. congolense parasites, which possess a larger array of related CBPs, also developed resistance to AN11736 through deletion within the locus. A genome-scale screen in T. brucei confirmed CBP loss-of-function as the primary mechanism of resistance and CRISPR-Cas9 editing proved that partial deletion within the locus was sufficient to confer resistance. CBP re-expression in either T. brucei or T. congolense AN11736-resistant lines restored drug-susceptibility. CBPs act by cleaving the benzoxaborole AN11736 to a carboxylic acid derivative, revealing a prodrug activation mechanism. Loss of CBP activity results in massive reduction in net uptake of AN11736, indicating that entry is facilitated by the concentration gradient created by prodrug metabolism.</p><p><br></p><p><strong>T. congolense assay</strong> is reported in the current study <a href='https://www.ebi.ac.uk/metabolights/MTBLS1309' rel='noopener noreferrer' target='_blank'><strong>MTBLS1309</strong></a>.</p><p><strong>T. brucei assay</strong> is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS1474' rel='noopener noreferrer' target='_blank'><strong>MTBLS1474</strong></a>.</p><p><br></p><p><strong>Linked cross omic data sets:</strong></p><p>Genome data associated with this study are available in the European Nucleotide Archive (ENA): accession number <a href='https://www.ebi.ac.uk/ena/browser/view/PRJEB34627' rel='noopener noreferrer' target='_blank'>PRJEB34627</a>.</p>
2020-10-22 | MTBLS1309 | MetaboLights
Project description:To investigate the mechanistic effects of UV irradiation on pea seedlings at the protein level, proteomic analyses were performed on pea seedlings irradiated daily with 0 and 10 min UV-B.
2023-05-04 | PXD038486 | Pride
Project description:Question Addresses: What is the gene expression profile from human umbilical vein endothelial cells (HUVEC) and human Jurkat T cells after irradiation (IR)? What, if any, is the effect of co-culturing these two cell types on gene expression? There are eight experimental conditions for this experiment: (1) non-irradiated HUVEC; (2) irradiated HUVEC; (3) non-irradiated Jurkat; (4) irradiated Jurkat; (5) non-irradiated HUVEC + non-irradiated Jurkat+; (6) non-irradiated HUVEC + irradiated Jurkat; (7) irradiated HUVEC + non-irradiated Jurkat; (8) irradiated HUVEC + irradiated Jurkat. A common, pooled reference consisting of RNA taken from conditions 1-8 as described above was used for all hybridizations.
2022-06-03 | GSE39019 | GEO