Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/32939
Title: Overexpression of eukaryotic initiation factor 5A (eIF5A) affects susceptibility to benznidazole in Trypanosoma cruzi populations
Authors: Moreira, Douglas de Souza
Duarte, Ana Paula
Pais, Fabiano Sviatopolk Mirsky
Pereira, Rosiane Aparecida da Silva
Romanha, Alvaro José
Schenkman, Sergio
Murta, Silvane Maria Fonseca
Affilliation: Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.
Universidade Federal de São Paulo. Departamento de Microbiologia, Imunologia e Parasitologia. São Paulo, SP, Brasil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.
Abstract: Eukaryotic 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.
Keywords: Trypanosoma cruzi
Drug resistance
Benznidazole
Eukaryotic initiation factor 5A (eIF5A)
keywords: Trypanosoma cruzi
Susceptibilidade
Resistência
Issue Date: 2018
Publisher: Fundação Oswaldo Cruz
Citation: MOREIRA, 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.
DOI: 10.1590/0074-02760180162
ISSN: 0074-0276
Copyright: open access
Appears in Collections:MG - IRR - Artigos de Periódicos

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