Academic Journal
Ribose 5-Phosphate Isomerase B Knockdown Compromises Trypanosoma brucei Bloodstream Form Infectivity
| العنوان: | Ribose 5-Phosphate Isomerase B Knockdown Compromises Trypanosoma brucei Bloodstream Form Infectivity |
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| المؤلفون: | Loureiro, I, Faria, J, Clayton, C, Macedo-Ribeiro, S, Santarém, N, Roy, N, Cordeiro-da-Siva, A, Tavares, J |
| المساهمون: | Instituto de Investigação e Inovação em Saúde |
| بيانات النشر: | Public Library of Science |
| سنة النشر: | 2015 |
| المجموعة: | Repositório Aberto da Universidade do Porto |
| مصطلحات موضوعية: | Aldose-Ketose Isomerases/genetics, Aldose-Ketose Isomerases/metabolism, Animals, Antibodies, Protozoan, Cloning, Molecular, Gene Expression Regulation, Enzymologic, Gene Knockdown Techniques, Mice, RNA Interference, Trypanosoma brucei brucei/enzymology, Trypanosoma brucei brucei/genetics, Trypanosoma brucei brucei/metabolism, Trypanosomiasis, African/blood, African/parasitology |
| الوصف: | 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. ; This work was funded by the European Community’s Seventh Framework Programme under grant agreement No. 602773 (Project KINDRED). The COST Action CM1307 ‘Targeted chemotherapy towards diseases caused by endoparasites’ and FEDER funds through the Operational Competitiveness Program – COMPETE and by National Funds through FCT – Fundação para a Ciência e a Tecnologia under the project PEstC/SAU/LA0002/2011 have also contributed for this work. IL and JF were supported by fellowships from FCT reference SFRH/BD/64528/2009 and SFRH/BD/79712/2011, respectively. NS is supported by a fellowship from the European Community’s Seventh Framework Programme under grant agreement No. 602773 (Project KINDRED). JT is an Investigator FCT funded by National funds through FCT and co-funded through ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1935-2727 |
| Relation: | info:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBD%2F64528%2F2009/PT; info:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBD%2F79712%2F2011/PT; PLoS Neglected Tropical Diseases, vol.9(1): e3430; https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0003430; https://repositorio-aberto.up.pt/handle/10216/118188 |
| DOI: | 10.1371/journal.pntd.0003430 |
| الاتاحة: | https://repositorio-aberto.up.pt/handle/10216/118188 https://doi.org/10.1371/journal.pntd.0003430 |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.D8C939DD |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 19352727 |
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| DOI: | 10.1371/journal.pntd.0003430 |