Trypanosoma brucei
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ABSTRACT:
PROVIDER: PRJNA133013 | ENA |
REPOSITORIES: ENA
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Project description:Mitochondrial metabolic remodeling is a hallmark of the Trypanosoma brucei digenetic life cycle since the insect stage utilizes the cost-effective oxidative phosphorylation to generate ATP, while bloodstream cells switch to less energetically efficient aerobic glycolysis. Due to difficulties in acquiring enough parasites from the tsetse fly vector for biochemical analysis, the dynamics of the parasite´s mitochondrial metabolic rewiring in the vector have remained obscure. Here, we took advantage of in vitro-induced differentiation to follow changes at the RNA levels.
2020-05-08 | GSE140796 | 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:Purpose: Acoziborole is a recently developed benzoxaborole class compound, currently in clinical trials, for stage 1 and stage 2 treatment of Human African Trypanosomiasis. Recent studies have made significant progress in determining the molecular mode of action of acoziborole. However, less is known about the potential mechanisms leading to acoziborole resistance in trypanosomes. By characterising in vitro drug-resistance, this study aimed to gain a better understanding of the mechanisms involved in acoziborole resistance in the clinicaly relevant Trypanosoma brucei Methods: Drug resistance was generated in vitro through incremental dosage of acoziborole. RNA was isolated from axenic cultures of drug-resistant and parental drug sensitive cells and submitted for RNA-seq Results: Transcriptomics analysis revealed widepread downregulation of transcripts associated with mammalian-infective bloodstream-form parasites. Conversely, transcripts associated with insect-stage procyclic form parasites were increased, indicating that the resistant cells had undergone an unspecified "differentiation event", albeit on a transcriptomic level Conclusions: Trypanosoma brucei resistance to acoziborole can be generated under in vitro axenic conditions, and "transcriptional differentiation" is a mechanism of resistance. However, it is unknown whether this phenomenon is relevant to an in vivo setting
2021-03-07 | GSE168394 | GEO
Project description:Mitochondrial DNA replication and gene expression are essential for cell survival. In Trypanosoma brucei, a protozoan animal and human parasite, the mitochondrial RNA polymerase (mtRNAP) plays roles in both transcription and DNA replication. This study identifies and characterizes the first mitochondrial transcription factor (mtTF1) in the Kinetoplastea. mtRNAP and mtTF1 form a high-molecular-weight complex that localizes to the kinetoplast DNA (kDNA) and is essential for parasite survival in both life cycle stages. Their localization is interdependent, and both proteins influence maxicircle replication, but not minicircle replication. Knockdown of either protein result in altered gene expression, particularly affecting the minor strand of the mitochondrial genome. Since mtTF1 is unique to the Kinetoplastea, it might prove to be a promising drug target.
2025-05-26 | GSE297664 | GEO
Project description:Glycolysis is the sole free-energy source for the deadly parasite Trypanosoma brucei and is therefore a possible target pathway for anti-trypanosomal drugs. Plasma-membrane glucose transport exerts high control over trypanosome glycolysis and hence the transporter is a promising drug target. Here we show that at high inhibitor concentrations, inhibition of trypanosome glucose transport causes cell death. Most interestingly, sublethal concentrations initiate a domino effect in which network adaptations enhance inhibition. total of 5 slides, including 3 biological replicates and dyeswap
2010-10-18 | E-GEOD-24275 | biostudies-arrayexpress
Project description:T. brucei PF cells were treated with several chemical reagents and anti-trypanosomatid drugs. The effect of each chemical perturbation on the transcriptome of T. brucei was examined by transcript profiling of treated vs. control cells. The results indicated widespread changes, suggesting that the transcriptome of T. brucei is highly responsive to environmental factors that perturb its metabolic and biological pathways.
2012-05-30 | GSE37593 | GEO
Project description:Effect of TbDRBD3 depletion on procyclic T. brucei transcriptome
| PRJNA101995 | ENA
Project description:African trypanosomiasis is still one of the infectious diseases threatening the health of human beings and animals, and severely impeding the continental economic development. Currently, the disease control programs are mainly relying on a limited number of parasiticides which are either expensive or with severe side-effect, and insecticides. In this study, we investigated the anti-trypanosome effect of two noble metal nanoclusters (NM-NCs), Ag2S-NC@MPA and AuNC@GSH. Both types of NCs can be efficiently up-taken by Trypanosoma brucei via a clathrin-dependent endocytosis pathway, and displayed dose-dependent anti-parasite effect by inducing apoptosis-associated organelle pathological alterations. The data not only revealed the clathrin-dependent endocytosis pathway in African trypanosome, but also proposed a new avenue for NM-NC-based drug development for trypanosomiasis.
2020-04-26 | PXD018801 |
Project description:Glycolysis is the sole free-energy source for the deadly parasite Trypanosoma brucei and is therefore a possible target pathway for anti-trypanosomal drugs. Plasma-membrane glucose transport exerts high control over trypanosome glycolysis and hence the transporter is a promising drug target. Here we show that at high inhibitor concentrations, inhibition of trypanosome glucose transport causes cell death. Most interestingly, sublethal concentrations initiate a domino effect in which network adaptations enhance inhibition.
2010-10-18 | GSE24275 | GEO
Project description:Dynamic mRNA Expression analysis of cells undergoing synchronous life-cycle differentiation in Trypanosoma brucei
| PRJNA117789 | ENA