Plasmodium falciparum
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PROVIDER: PRJNA261419 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Plasmodium parasites mount an arrest response against dihydroartemisinin [P. falciparum RNA-Seq]
| PRJNA263263 | ENA
Project description:Plasmodium parasites mount an arrest response against dihydroartemisinin [P. berghei RNA-Seq]
| PRJNA263264 | ENA
Project description:Control of malaria is threatened by emerging parasite resistance to artemisinin drug (ART) therapies. The molecular details of how Plasmodium malaria parasites response to ART and how this relates to resistance is not clear. To determine how parasites respond to ART by altering gene expression, we performed a transcriptomic study of dihydroartemisinin (DHA) response in P. falciparum K1 strain and in P. berghei ANKA strain. Microarray data from DHA-treated P. falciparum trophozoite stage parasites were compared with data from other ART treatments. Genes with consistent changes in expression were identified, which includes notably down-regulation of cytosolic ribosomal protein genes. RNA-seq data revealed a similar pattern of transcriptomic change, although the pattern was much clearer in that more than one-third of P. falciparum trophozoite genes are differentially expressed with greater statistical support for down-regulation of ribosomal protein genes. The poor overlap of differentially-expressed genes between microarray and RNA-seq and less-well defined patterns for the former suggests that the accuracy of microarray is limited by technological bias. The trophozoite response to DHA is overall “ring-like” and less “trophozoite-like”, which is consistent with previous findings that Plasmodium can enter a quiescent ring-like state to resist ART. RNA-seq data from DHA-treated P. falciparum rings reveal a more muted response, although there is considerable overlap of differentially expressed genes with DHA-treated trophozoites. In contrast, P. falciparum schizonts are unresponsive to DHA, suggesting that the protective response acts mainly to arrest parasite development through the G2/M checkpoint. The transcriptional response of P. berghei to DHA treatment in vivo in infected mice is strikingly similar to the P. falciparum in vitro ring and trophozoite responses, in which ribosomal protein genes are notably down-regulated. These results suggest Plasmodium species respond to DHA in the same way. This knowledge could be applied to outwit the parasite to deliver more effective artemisinin therapies, and maybe hinder the development of drug resistance.
2015-10-15 | GSE62132 | GEO
Project description:Control of malaria is threatened by emerging parasite resistance to artemisinin drug (ART) therapies. The molecular details of how Plasmodium malaria parasites response to ART and how this relates to resistance is not clear. To determine how parasites respond to ART by altering gene expression, we performed a transcriptomic study of dihydroartemisinin (DHA) response in P. falciparum K1 strain and in P. berghei ANKA strain. Microarray data from DHA-treated P. falciparum trophozoite stage parasites were compared with data from other ART treatments. Genes with consistent changes in expression were identified, which includes notably down-regulation of cytosolic ribosomal protein genes. RNA-seq data revealed a similar pattern of transcriptomic change, although the pattern was much clearer in that more than one-third of P. falciparum trophozoite genes are differentially expressed with greater statistical support for down-regulation of ribosomal protein genes. The poor overlap of differentially-expressed genes between microarray and RNA-seq and less-well defined patterns for the former suggests that the accuracy of microarray is limited by technological bias. The trophozoite response to DHA is overall âring-likeâ and less âtrophozoite-likeâ, which is consistent with previous findings that Plasmodium can enter a quiescent ring-like state to resist ART. RNA-seq data from DHA-treated P. falciparum rings reveal a more muted response, although there is considerable overlap of differentially expressed genes with DHA-treated trophozoites. In contrast, P. falciparum schizonts are unresponsive to DHA, suggesting that the protective response acts mainly to arrest parasite development through the G2/M checkpoint. The transcriptional response of P. berghei to DHA treatment in vivo in infected mice is strikingly similar to the P. falciparum in vitro ring and trophozoite responses, in which ribosomal protein genes are notably down-regulated. These results suggest Plasmodium species respond to DHA in the same way. This knowledge could be applied to outwit the parasite to deliver more effective artemisinin therapies, and maybe hinder the development of drug resistance. Two condition drug-treatment experiment, Dihydroartemisinin vs. Vehicle control treatment with matched reference untreated controls. Biological replicates: 5 independently grown and harvested experimental culture replicates. One replicate of treatment/reference time-point per array.
2015-10-15 | E-GEOD-61536 | biostudies-arrayexpress
Project description:Abstract: The mitochondrial electron transport chain is essential to Plasmodium and is the target of the antimalarial drug atovaquone. The mitochondrial genomes of Plasmodium sp. are the most reduced known, and the majority of mitochondrial proteins are encoded in the nucleus and imported into the mitochondrion post-translationally. Many organisms have signalling pathways between the mitochondria and the nucleus to regulate the expression of nuclear-encoded mitochondrially-targeted proteins, for example in response to mitochondrial dysfunction. We have studied the gene expression profiles of synchronous Plasmodium falciparum treated with an LD50 concentration of the complex III inhibitor antimycin A, to investigate whether such pathways exist in the parasite. There was a broad perturbation of gene expression. Some effects were attributable to a delay in the gene expression phase of drug-treated parasites. However, our data also indicated regulation of mitochondrial stress response genes and genes involved in pyrimidine biosynthesis. 3 biological replicates each for treated and untreated: control (1/2000 DMSO) and LD50 antimycin A, respectively. Normalised microarray data for antimycin A-treated parasites were contrasted against untreated (DMSO) controls.
2012-04-19 | E-GEOD-28625 | biostudies-arrayexpress
Project description:Artemisinin and its derivatives exert the potent, antimalarial action, although the mechanisms by which these drugs inhibit the growth of mararia parasites is not fully understood. We used microarrays to detail the global gene expression change in early erythrocytic P. falciparum, and identified molecules that may contribute to the activity of dihydroartemisinin.
2020-11-30 | GSE160666 | GEO
Project description:The ubiquitin-conjugating enzyme 13 (Ubc13) has an essential function and putative role in artemisinin activity against Plasmodium falciparum. Ubc13 conjugates lysine 63-linked ubiquitin (K63-Ub) to proteins, but the role of this modification in Plasmodium remains largely unknown. Herein, we characterize and deploy NSC697923 to interrogate PfUbc13 function. We demonstrate that NSC697923 covalently targets the PfUbc13 active site residue and exhibits nanomolar inhibitory potency. NSC697923 displays anti-Plasmodium activity against drug-sensitive and drug-resistant asexual strains, gametocytes, and liver stage parasites, and synergizes with the malaria drug dihydroartemisinin. NSC697923 specifically reduces K63-Ub levels in asexual blood stage parasites, and subsequent ubiquitin pull-down assays and proteomic analyses identified putative PfUbc13 substrates. We highlight 37 proteins that overlapped with two previous ubiquitin datasets and were enriched in translation, transcription, and proteasome processes. A cellular puromycin-incorporation study demonstrated reduction of P. falciparum nascent protein synthesis following NSC697923 exposure, supporting a role for PfUbc13 and K63-Ub in mediating parasite protein translation. These findings expand our knowledge of the PfUbc13-dependent processes in these pathogenic parasites and highlight this enzyme as a potential antimalarial drug target.
2025-04-29 | PXD059643 | Pride
Project description:Control of malaria is threatened by emerging parasite resistance to artemisinin drug (ART) therapies. The molecular details of how Plasmodium malaria parasites response to ART and how this relates to resistance is not clear. To determine how parasites respond to ART by altering gene expression, we performed a transcriptomic study of dihydroartemisinin (DHA) response in P. falciparum K1 strain and in P. berghei ANKA strain. Microarray data from DHA-treated P. falciparum trophozoite stage parasites were compared with data from other ART treatments. Genes with consistent changes in expression were identified, which includes notably down-regulation of cytosolic ribosomal protein genes. RNA-seq data revealed a similar pattern of transcriptomic change, although the pattern was much clearer in that more than one-third of P. falciparum trophozoite genes are differentially expressed with greater statistical support for down-regulation of ribosomal protein genes. The poor overlap of differentially-expressed genes between microarray and RNA-seq and less-well defined patterns for the former suggests that the accuracy of microarray is limited by technological bias. The trophozoite response to DHA is overall “ring-like” and less “trophozoite-like”, which is consistent with previous findings that Plasmodium can enter a quiescent ring-like state to resist ART. RNA-seq data from DHA-treated P. falciparum rings reveal a more muted response, although there is considerable overlap of differentially expressed genes with DHA-treated trophozoites. In contrast, P. falciparum schizonts are unresponsive to DHA, suggesting that the protective response acts mainly to arrest parasite development through the G2/M checkpoint. The transcriptional response of P. berghei to DHA treatment in vivo in infected mice is strikingly similar to the P. falciparum in vitro ring and trophozoite responses, in which ribosomal protein genes are notably down-regulated. These results suggest Plasmodium species respond to DHA in the same way. This knowledge could be applied to outwit the parasite to deliver more effective artemisinin therapies, and maybe hinder the development of drug resistance.
2015-10-15 | GSE61536 | GEO
Project description:Control of malaria is threatened by emerging parasite resistance to artemisinin drug (ART) therapies. The molecular details of how Plasmodium malaria parasites response to ART and how this relates to resistance is not clear. To determine how parasites respond to ART by altering gene expression, we performed a transcriptomic study of dihydroartemisinin (DHA) response in P. falciparum K1 strain and in P. berghei ANKA strain. Microarray data from DHA-treated P. falciparum trophozoite stage parasites were compared with data from other ART treatments. Genes with consistent changes in expression were identified, which includes notably down-regulation of cytosolic ribosomal protein genes. RNA-seq data revealed a similar pattern of transcriptomic change, although the pattern was much clearer in that more than one-third of P. falciparum trophozoite genes are differentially expressed with greater statistical support for down-regulation of ribosomal protein genes. The poor overlap of differentially-expressed genes between microarray and RNA-seq and less-well defined patterns for the former suggests that the accuracy of microarray is limited by technological bias. The trophozoite response to DHA is overall “ring-like” and less “trophozoite-like”, which is consistent with previous findings that Plasmodium can enter a quiescent ring-like state to resist ART. RNA-seq data from DHA-treated P. falciparum rings reveal a more muted response, although there is considerable overlap of differentially expressed genes with DHA-treated trophozoites. In contrast, P. falciparum schizonts are unresponsive to DHA, suggesting that the protective response acts mainly to arrest parasite development through the G2/M checkpoint. The transcriptional response of P. berghei to DHA treatment in vivo in infected mice is strikingly similar to the P. falciparum in vitro ring and trophozoite responses, in which ribosomal protein genes are notably down-regulated. These results suggest Plasmodium species respond to DHA in the same way. This knowledge could be applied to outwit the parasite to deliver more effective artemisinin therapies, and maybe hinder the development of drug resistance.
2015-10-15 | GSE62133 | GEO