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

Author(s)

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]

Affiliation

^[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

• Document type: Journal article
• Source: Memórias do Instituto Oswaldo Cruz; v. 113, n. 9 2018.
• Web of Science Citations: 0

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 (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)

• FAPESP's process: 15/22031-0 - Cell signaling in Trypanosoma during host-parasite interaction
• Grantee: Sergio Schenkman
• Support Opportunities: Research Projects - Thematic Grants