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

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....

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Autores principales: Hickson, Jéssica, Athayde, Lucas Felipe Almeida, Miranda, Thainá Godinho, Junior, Policarpo Ademar Sales, dos Santos, Anderson Coqueiro, da Cunha Galvão, Lúcia Maria, da Câmara, Antônia Cláudia Jácome, Bartholomeu, Daniella Castanheira, de Souza, Rita de Cássia Moreira, Murta, Silvane Maria Fonseca, Nahum, Laila Alves
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9169349/
https://www.ncbi.nlm.nih.gov/pubmed/35668508
http://dx.doi.org/10.1186/s13071-022-05319-2
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author Hickson, Jéssica
Athayde, Lucas Felipe Almeida
Miranda, Thainá Godinho
Junior, Policarpo Ademar Sales
dos Santos, Anderson Coqueiro
da Cunha Galvão, Lúcia Maria
da Câmara, Antônia Cláudia Jácome
Bartholomeu, Daniella Castanheira
de Souza, Rita de Cássia Moreira
Murta, Silvane Maria Fonseca
Nahum, Laila Alves
author_facet Hickson, Jéssica
Athayde, Lucas Felipe Almeida
Miranda, Thainá Godinho
Junior, Policarpo Ademar Sales
dos Santos, Anderson Coqueiro
da Cunha Galvão, Lúcia Maria
da Câmara, Antônia Cláudia Jácome
Bartholomeu, Daniella Castanheira
de Souza, Rita de Cássia Moreira
Murta, Silvane Maria Fonseca
Nahum, Laila Alves
author_sort Hickson, Jéssica
collection PubMed
description 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. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13071-022-05319-2.
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spelling pubmed-91693492022-06-07 Trypanosoma cruzi iron superoxide dismutases: insights from phylogenetics to chemotherapeutic target assessment Hickson, Jéssica Athayde, Lucas Felipe Almeida Miranda, Thainá Godinho Junior, Policarpo Ademar Sales dos Santos, Anderson Coqueiro da Cunha Galvão, Lúcia Maria da Câmara, Antônia Cláudia Jácome Bartholomeu, Daniella Castanheira de Souza, Rita de Cássia Moreira Murta, Silvane Maria Fonseca Nahum, Laila Alves Parasit Vectors Research 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. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13071-022-05319-2. BioMed Central 2022-06-06 /pmc/articles/PMC9169349/ /pubmed/35668508 http://dx.doi.org/10.1186/s13071-022-05319-2 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Hickson, Jéssica
Athayde, Lucas Felipe Almeida
Miranda, Thainá Godinho
Junior, Policarpo Ademar Sales
dos Santos, Anderson Coqueiro
da Cunha Galvão, Lúcia Maria
da Câmara, Antônia Cláudia Jácome
Bartholomeu, Daniella Castanheira
de Souza, Rita de Cássia Moreira
Murta, Silvane Maria Fonseca
Nahum, Laila Alves
Trypanosoma cruzi iron superoxide dismutases: insights from phylogenetics to chemotherapeutic target assessment
title Trypanosoma cruzi iron superoxide dismutases: insights from phylogenetics to chemotherapeutic target assessment
title_full Trypanosoma cruzi iron superoxide dismutases: insights from phylogenetics to chemotherapeutic target assessment
title_fullStr Trypanosoma cruzi iron superoxide dismutases: insights from phylogenetics to chemotherapeutic target assessment
title_full_unstemmed Trypanosoma cruzi iron superoxide dismutases: insights from phylogenetics to chemotherapeutic target assessment
title_short Trypanosoma cruzi iron superoxide dismutases: insights from phylogenetics to chemotherapeutic target assessment
title_sort trypanosoma cruzi iron superoxide dismutases: insights from phylogenetics to chemotherapeutic target assessment
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9169349/
https://www.ncbi.nlm.nih.gov/pubmed/35668508
http://dx.doi.org/10.1186/s13071-022-05319-2
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