Overexpression of cytoplasmic TcSIR2RP1 and mitochondrial TcSIR2RP3 impacts on Trypanosoma cruzi growth and cell invasion

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dc.citation.titlePLOS Neglected Tropical Diseases
dc.citation.volume1-22
dc.creatorRitagliati, Carla
dc.creatorAlonso, Victoria Lucía
dc.creatorManarin, Romina
dc.creatorCribb, Pamela
dc.creatorSerra, Esteban Carlos
dc.date.accessioned2024-04-22T14:24:22Z
dc.date.available2024-04-22T14:24:22Z
dc.date.issued2015-04-15
dc.description.abstractAbstract Background Trypanosoma cruzi is a protozoan pathogen responsible for Chagas disease. Current therapies are inadequate because of their severe host toxicity and numerous side effects. The identification of new biotargets is essential for the development of more efficient therapeutic alternatives. Inhibition of sirtuins from Trypanosoma brucei and Leishmania ssp. Showed promising results, indicating that these enzymes may be considered as targets for drug discovery in parasite infection. Here, we report the first characterization of the two sirtuins present in T. cruzi. Methodology Dm28c epimastigotes that inducibly overexpress TcSIR2RP1 and TcSIR2RP3 were constructed and used to determine their localizations and functions. These transfected lines were tested regarding their acetylation levels, proliferation and metacyclogenesis rate, viability when treated with sirtuin inhibitors and in vitro infectivity. Conclusion TcSIR2RP1 and TcSIR2RP3 are cytosolic and mitochondrial proteins respectively. Our data suggest that sirtuin activity is important for the proliferation of T. cruzi replicative forms, for the host cell-parasite interplay, and for differentiation among life-cycle stages; but each one performs different roles in most of these processes. Our results increase the knowledge on the localization and function of these enzymes, and the overexpressing T. cruzi strains we obtained can be useful tools for experimental screening of trypanosomatid sirtuin inhibitors.
dc.description.filFil: Ritagliati, Carla. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología Molecular y Celular de Rosario (CONICET-IBR); Argentina.
dc.description.filFil: Alonso, Victoria Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología Molecular y Celular de Rosario (CONICET-IBR); Argentina.
dc.description.filFil: Alonso, Victoria Lucía. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina.
dc.description.filFil: Manarin, Romina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina.
dc.description.filFil: Cribb, Pamela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología Molecular y Celular de Rosario (CONICET-IBR); Argentina.
dc.description.filFil: Cribb, Pamela. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina.
dc.description.filFil: Serra, Esteban Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología Molecular y Celular de Rosario (CONICET-IBR); Argentina.
dc.description.filFil: Serra, Esteban Carlos. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; Argentina.
dc.description.sponsorshipConsejo Nacional de Investigaciones Científicas y Técnicas (CONICET): PIP2010 0685
dc.identifier.issn1935-2735
dc.identifier.urihttps://hdl.handle.net/2133/26919
dc.language.isoen
dc.publisherPublic Library of Science (PLOS)
dc.relation.publisherversionhttps://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0003725#abstract0
dc.relation.publisherversionhttps://doi.org/10.1371/journal.pntd.0003725
dc.rightsopenAccess
dc.rights.holderRitagliati, Carla
dc.rights.holderAlonso, Victoria Lucía
dc.rights.holderManarin, Romina
dc.rights.holderCribb, Pamela
dc.rights.holderSerra, Esteban Carlos
dc.rights.holderUniversidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas
dc.rights.textAttribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectAcetylation
dc.subjectChagas disease
dc.subjectDrug discovery
dc.subjectHost-parasite
dc.subjectLeishmania
dc.subjectLife cycle stages
dc.subjectTrypanosoma cruzi
dc.titleOverexpression of cytoplasmic TcSIR2RP1 and mitochondrial TcSIR2RP3 impacts on Trypanosoma cruzi growth and cell invasion
dc.typearticulo
dc.type.versionpublishedVersion

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