Corrigendum to 'the anti-fecundity effect of 5-azacytidine (5-AzaC) on Schistosoma mansoni is linked to dis-regulated transcription, translation and stem cell activities' [Int. J. Parasitol. Drugs and Drug Resist. 8 (2018) 213-222]
| Autor: | Michael Squance, Kathrin K. Geyer, Daniel Berrar, Martin T. Swain, Toby Wilkinson, Karl F. Hoffmann, Cristian Chaparro, Martin Vickers, Sabrina E. Munshi |
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| Rok vydání: | 2018 |
| Předmět: |
Pharmacology
Drug media_common.quotation_subject INT 5-Azacytidine Schistosoma mansoni Stem cells Biology biology.organism_classification Fecundity Molecular biology Article Infectious Diseases Transcription (biology) Pharmacology (medical) Parasitology Epigenetics RNA-Seq Stem cell Protein synthesis media_common |
| Zdroj: | International Journal for Parasitology: Drugs and Drug Resistance Geyer, K K, Munshi, S E, Vickers, M, Squance, M, Wilkinson, T J, Berrar, D, Chaparro, C, Swain, M T & Hoffmann, K F 2018, ' Corrigendum to 'the anti-fecundity effect of 5-azacytidine (5-AzaC) on Schistosoma mansoni is linked to dis-regulated transcription, translation and stem cell activities' [Int. J. Parasitol. Drugs and Drug Resist. 8 (2018) 213-222] ', International Journal for Parasitology: Drugs and Drug Resistance . https://doi.org/10.1016/j.ijpddr.2018.07.002 |
| ISSN: | 2211-3207 |
| DOI: | 10.1016/j.ijpddr.2018.07.002 |
| Popis: | Uncontrolled host immunological reactions directed against tissue-trapped eggs precipitate a potentially lethal, pathological cascade responsible for schistosomiasis. Blocking schistosome egg production, therefore, presents a strategy for simultaneously reducing immunopathology as well as limiting disease transmission in endemic or emerging areas. We recently demonstrated that the ribonucleoside analogue 5-azacytidine (5-AzaC) inhibited Schistosoma mansoni oviposition, egg maturation and ovarian development. While these anti-fecundity effects were associated with a loss of DNA methylation, other molecular processes affected by 5-AzaC were not examined at the time. By comparing the transcriptomes of 5-AzaC-treated females to controls, we provide evidence that this ribonucleoside analogue also modulates other crucial aspects of schistosome egg-laying biology. For example, S. mansoni gene products associated with amino acid-, carbohydrate-, fatty acid-, nucleotide- and tricarboxylic acid (TCA)- homeostasis are all dysregulated in 5-AzaC treated females. To validate the metabolic pathway most significantly affected by 5-AzaC, amino acid metabolism, nascent protein synthesis was subsequently quantified in adult schistosomes. Here, 5-AzaC inhibited this process by 68% ±16.7% (SEM) in male- and 81% ±4.8% (SEM) in female-schistosomes. Furthermore, the transcriptome data indicated that adult female stem cells were also affected by 5-AzaC. For instance, 40% of transcripts associated with proliferating schistosome cells were significantly down-regulated by 5-AzaC. This finding correlated with a considerable reduction (95%) in the number of 5-ethynyl-2′-deoxyuridine (EdU) positive cells found in 5-AzaC-treated females. In addition to protein coding genes, the effect that 5-AzaC had on repetitive element expression was also assessed. Here, 46 repeats were found differentially transcribed between 5-AzaC-treated and control females with long terminal repeat (LTR) and DNA transposon classes being amongst the most significant. This study demonstrates that the anti-fecundity activity of 5-AzaC affects more than just DNA methylation in schistosome parasites. Further characterisation of these processes may reveal novel targets for schistosomiasis control. Graphical abstract Image 1 Highlights • The ribonucleoside 5-azacytidine (5-AzaC) inhibits schistosome egg production. • 5-AzaC modulates schistosome transcription and translation. • Schistosome stem cell proliferation and maintenance are affected by 5-AzaC. |
| Databáze: | OpenAIRE |
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