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

Abstract

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

Selection, Identification, and Transcript Expression Analysis of Antioxidant Enzyme Genes in Neoseiulus barkeri after Short-Term Heat Stress

“…Based on the analysis of multiple sequence alignment, NbSOD is categorized as a member of the Fe-Mn SOD family based on the presence of two domains specific to the Fe-Mn SOD family: Mn/Fe-N and Mn/Fe-C (Figure 3A). Due to the presence of iron sod (FeSOD) in prokaryotes and plants [34,35] and manganese sod (MnSOD) in eukaryotes [36], NbSOD is classified as MnSOD. NbPrx was classified as one of the 1-Cys peroxiredoxins due to the presence of a single conserved Cys residue at position 47 (Figure 3B) [37,38].…”

TriTrypDB: An integrated functional genomics resource for kinetoplastida

“…Below are a few recent examples of how TriTrypDB data and tools have been utilized by the research community to conduct their own research. TriTrypDB genomes and annotations have been used to characterize individual genes [69][70][71][72][73] or gene families [74,75], identify orthologs across species [55,70,76], conduct genome-wide analyses to study genetic variations such as SNPs, CNVs and hybridization events [77][78][79], perform comparative genomic [80][81][82] and phylogenetic/ phylogenomic [82,83] analyses, and as reference genomes for the assembly and/or annotation of newly generated genomes [16,84]. Similarly, the genome assemblies and annotations have also been utilized for the analysis of differential gene expression [19,72,85], protein expression [85][86][87], the identification of post-translational modifications [72] and potential new genes missing in the official gene sets [88].…”