Trypanosoma cruzi iron superoxide dismutases: insights from phylogenetics to chemotherapeutic target assessment.

Autor: Hickson J; René Rachou Institute, Oswaldo Cruz Foundation (Functional genomics of parasites group; Biosystems informatics, bioengineering and genomic group), Belo Horizonte, Minas Gerais, Brazil., Athayde LFA; René Rachou Institute, Oswaldo Cruz Foundation (Functional genomics of parasites group; Biosystems informatics, bioengineering and genomic group), Belo Horizonte, Minas Gerais, Brazil.; Department of Genetics, Ecology and Evolution, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil., Miranda TG; René Rachou Institute, Oswaldo Cruz Foundation (Functional genomics of parasites group; Biosystems informatics, bioengineering and genomic group), Belo Horizonte, Minas Gerais, Brazil.; Department of Genetics, Ecology and Evolution, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil., Junior PAS; René Rachou Institute, Oswaldo Cruz Foundation (Functional genomics of parasites group; Biosystems informatics, bioengineering and genomic group), Belo Horizonte, Minas Gerais, Brazil., Dos Santos AC; Department of Genetics, Ecology and Evolution, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil., da Cunha Galvão LM; Department of Genetics, Ecology and Evolution, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil.; Department of Clinical and Toxicological Analysis, Federal University of Rio Grande do Norte State, Natal, Rio Grande do Norte, Brazil., da Câmara ACJ; Department of Clinical and Toxicological Analysis, Federal University of Rio Grande do Norte State, Natal, Rio Grande do Norte, Brazil., Bartholomeu DC; Department of Genetics, Ecology and Evolution, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil., de Souza RCM; René Rachou Institute, Oswaldo Cruz Foundation (Functional genomics of parasites group; Biosystems informatics, bioengineering and genomic group), Belo Horizonte, Minas Gerais, Brazil., Murta SMF; René Rachou Institute, Oswaldo Cruz Foundation (Functional genomics of parasites group; Biosystems informatics, bioengineering and genomic group), Belo Horizonte, Minas Gerais, Brazil. silvane.murta@fiocruz.br., Nahum LA; René Rachou Institute, Oswaldo Cruz Foundation (Functional genomics of parasites group; Biosystems informatics, bioengineering and genomic group), Belo Horizonte, Minas Gerais, Brazil. laila.nahum@fiocruz.br.; Department of Genetics, Ecology and Evolution, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil. laila.nahum@fiocruz.br.; Promove College of Technology, Belo Horizonte, Minas Gerais, Brazil. laila.nahum@fiocruz.br.
Jazyk: angličtina
Zdroj: Parasites & vectors [Parasit Vectors] 2022 Jun 06; Vol. 15 (1), pp. 194. Date of Electronic Publication: 2022 Jun 06.
DOI: 10.1186/s13071-022-05319-2
Abstrakt: Background: Components of the antioxidant defense system in Trypanosoma cruzi are potential targets for new drug development. Superoxide dismutases (SODs) constitute key components of antioxidant defense systems, removing excess superoxide anions by converting them into oxygen and hydrogen peroxide. The main goal of the present study was to investigate the genes coding for iron superoxide dismutase (FeSOD) in T. cruzi strains from an evolutionary perspective.
Methods: In this study, molecular biology methods and phylogenetic studies were combined with drug assays. The FeSOD-A and FeSOD-B genes of 35 T. cruzi strains, belonging to six discrete typing units (Tcl-TcVI), from different hosts and geographical regions were amplified by PCR and sequenced using the Sanger method. Evolutionary trees were reconstructed based on Bayesian inference and maximum likelihood methods. Drugs that potentially interacted with T. cruzi FeSODs were identified and tested against the parasites.
Results: Our results suggest that T. cruzi FeSOD types are members of distinct families. Gene copies of FeSOD-A (n = 2), FeSOD-B (n = 4) and FeSOD-C (n = 4) were identified in the genome of the T. cruzi reference clone CL Brener. Phylogenetic inference supported the presence of two functional variants of each FeSOD type across the T. cruzi strains. Phylogenetic trees revealed a monophyletic group of FeSOD genes of T. cruzi TcIV strains in both distinct genes. Altogether, our results support the hypothesis that gene duplication followed by divergence shaped the evolution of T. cruzi FeSODs. Two drugs, mangafodipir and polaprezinc, that potentially interact with T. cruzi FeSODs were identified and tested in vitro against amastigotes and trypomastigotes: mangafodipir had a low trypanocidal effect and polaprezinc was inactive.
Conclusions: Our study contributes to a better understanding of the molecular biodiversity of T. cruzi FeSODs. Herein we provide a successful approach to the study of gene/protein families as potential drug targets.
(© 2022. The Author(s).)
Databáze: MEDLINE
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