Overexpression of eukaryotic initiation factor 5A (eIF5A) affects susceptibility to benznidazole in Trypanosoma cruzi populations

dc.creatorMoreira, Douglas de Souza
dc.creatorDuarte, Ana Paula
dc.creatorPais, Fabiano Sviatopolk Mirsky
dc.creatorPereira, Rosiane Aparecida da Silva
dc.creatorRomanha, Alvaro José
dc.creatorSchenkman, Sergio
dc.creatorMurta, Silvane Maria Fonseca
dc.date2019-05-06T12:19:13Z
dc.date2019-05-06T12:19:13Z
dc.date2018
dc.date.accessioned2023-09-26T21:44:03Z
dc.date.available2023-09-26T21:44:03Z
dc.identifierMOREIRA, Douglas de Souza et al. Overexpression of eukaryotic initiation factor 5A (eIF5A) affects susceptibility to benznidazole in Trypanosoma cruzi populations. Memórias do Instituto Oswaldo Cruz, Rio de Janeiro, v. 113, n. 9, p. 1-5, 2018.
dc.identifier0074-0276
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/32939
dc.identifier10.1590/0074-02760180162
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8873406
dc.descriptionEukaryotic initiation factor 5A (eIF5A) is a conserved protein with an essential role in translation elongation. Using one and two-dimensional western blotting, we showed that the eIF5A protein level was 2-fold lower in benznidazole (BZ)-resistant (BZR and 17LER) Trypanosoma cruzi populations than in their respective susceptible counterparts (BZS and 17WTS). To confirm the role of eIF5A in BZ resistance, we transfected BZS and 17WTS with the wild-type eIF5A or mutant eIF5A-S2A (in which serine 2 was replaced by alanine). Upon overexpressing eIF5A, both susceptible lines became approximately 3- and 5-fold more sensitive to BZ. In contrast, the eIF5A-S2A mutant did not alter its susceptibility to BZ. These data suggest that BZ resistance might arise from either decreasing the translation of proteins that require eIF5A, or as a consequence of differential levels of precursors for the hypusination reactions (e.g., spermidine and trypanothione), both of which alter BZ’s effects in the parasite.
dc.formatapplication/pdf
dc.languageeng
dc.publisherFundação Oswaldo Cruz
dc.rightsopen access
dc.subjectTrypanosoma cruzi
dc.subjectSusceptibilidade
dc.subjectResistência
dc.subjectTrypanosoma cruzi
dc.subjectDrug resistance
dc.subjectBenznidazole
dc.subjectEukaryotic initiation factor 5A (eIF5A)
dc.titleOverexpression of eukaryotic initiation factor 5A (eIF5A) affects susceptibility to benznidazole in Trypanosoma cruzi populations
dc.typeArticle


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