Overexpression of eukaryotic initiation factor 5A (eIF5A) affects susceptibility to benznidazole in Trypanosoma cruzi populations
Mem. Inst. Oswaldo Cruz
;
113(9): e180162, 2018. graf
Artigo
em Inglês
| LILACS
| ID: biblio-1040603
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.
Texto completo:
DisponíveL
Índice:
LILACS (Américas)
Assunto principal:
Tripanossomicidas
/
Trypanosoma cruzi
/
Resistência a Medicamentos
/
Fatores de Iniciação de Peptídeos
/
Proteínas de Ligação a RNA
/
Nitroimidazóis
Limite:
Humanos
Idioma:
Inglês
Revista:
Mem. Inst. Oswaldo Cruz
Assunto da revista:
Medicina Tropical
/
Parasitologia
Ano de publicação:
2018
Tipo de documento:
Artigo
País de afiliação:
Brasil
Instituição/País de afiliação:
Fundação Oswaldo Cruz-Fiocruz/BR
/
Universidade Federal de São Paulo/BR
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