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

Autor(es)

Moreira, Douglas de Souza ^[1] ; Duarte, Ana Paula ^[1] ; Mirsky Pais, Fabiano Sviatopolk ^[1] ; da Silva-Pereira, Rosiane Aparecida ^[1] ; Romanha, Alvaro Jose ^[1] ; Schenkman, Sergio ^[2] ; Fonseca Murta, Silvane Maria ^[1]

Afiliação do(s) autor(es)

^[1] Inst Rene Rachou, Fundacao Oswaldo Cruz Fiocruz, Belo Horizonte, MG - Brazil

^[2] Univ Fed Sao Paulo, Dept Microbiol Imunol & Parasitol, Sao Carlos, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Memórias do Instituto Oswaldo Cruz; v. 113, n. 9 2018.
• Citações Web of Science: 0

Resumo

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 (B7R 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. (AU)

• Processo FAPESP: 15/22031-0 - Sinalização celular em Trypanosoma durante a interação do parasita com o hospedeiro
• Beneficiário: Sergio Schenkman
• Modalidade de apoio: Auxílio à Pesquisa - Temático