Ribose 5-phosphate isomerase B knockdown compromises trypanosoma brucei bloodstream form infectivity
Ribose 5-phosphate isomerase is an enzyme involved in the non-oxidative branch of the pentose phosphate pathway, and catalyzes the inter-conversion of D-ribose 5-phosphate and D-ribulose 5-phosphate. Trypanosomatids, including the agent of African sleeping sickness namely Trypanosoma brucei, have a...
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| Hauptverfasser: | , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
January 8, 2015
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| In: |
PLoS neglected tropical diseases
Year: 2015, Jahrgang: 9, Heft: 1 |
| ISSN: | 1935-2735 |
| DOI: | 10.1371/journal.pntd.0003430 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1371/journal.pntd.0003430 Verlag, lizenzpflichtig, Volltext: https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0003430 
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| Verfasserangaben: | Inês Loureiro, Joana Faria, Christine Clayton, Sandra Macedo-Ribeiro, Nuno Santarém, Nilanjan Roy, Anabela Cordeiro-da-Siva, Joana Tavares |
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| 245 | 1 | 0 | |a Ribose 5-phosphate isomerase B knockdown compromises trypanosoma brucei bloodstream form infectivity |c Inês Loureiro, Joana Faria, Christine Clayton, Sandra Macedo-Ribeiro, Nuno Santarém, Nilanjan Roy, Anabela Cordeiro-da-Siva, Joana Tavares |
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| 520 | |a Ribose 5-phosphate isomerase is an enzyme involved in the non-oxidative branch of the pentose phosphate pathway, and catalyzes the inter-conversion of D-ribose 5-phosphate and D-ribulose 5-phosphate. Trypanosomatids, including the agent of African sleeping sickness namely Trypanosoma brucei, have a type B ribose-5-phosphate isomerase. This enzyme is absent from humans, which have a structurally unrelated ribose 5-phosphate isomerase type A, and therefore has been proposed as an attractive drug target waiting further characterization. In this study, Trypanosoma brucei ribose 5-phosphate isomerase B showed in vitro isomerase activity. RNAi against this enzyme reduced parasites' in vitro growth, and more importantly, bloodstream forms infectivity. Mice infected with induced RNAi clones exhibited lower parasitaemia and a prolonged survival compared to control mice. Phenotypic reversion was achieved by complementing induced RNAi clones with an ectopic copy of Trypanosoma cruzi gene. Our results present the first functional characterization of Trypanosoma brucei ribose 5-phosphate isomerase B, and show the relevance of an enzyme belonging to the non-oxidative branch of the pentose phosphate pathway in the context of Trypanosoma brucei infection. | ||
| 650 | 4 | |a Bloodstream infections | |
| 650 | 4 | |a Cloning | |
| 650 | 4 | |a Isomerases | |
| 650 | 4 | |a Parasitic diseases | |
| 650 | 4 | |a Ribose | |
| 650 | 4 | |a RNA interference | |
| 650 | 4 | |a Trypanosoma | |
| 650 | 4 | |a Trypanosoma brucei gambiense | |
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| 700 | 1 | |a Clayton, Christine |e VerfasserIn |0 (DE-588)1098447158 |0 (DE-627)85763335X |0 (DE-576)469125624 |4 aut | |
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| 700 | 1 | |a Santarém, Nuno |e VerfasserIn |4 aut | |
| 700 | 1 | |a Roy, Nilanjan |e VerfasserIn |4 aut | |
| 700 | 1 | |a Cordeiro-da-Siva, Anabela |e VerfasserIn |4 aut | |
| 700 | 1 | |a Tavares, Joana |e VerfasserIn |4 aut | |
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