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dc.contributor.authorMontenegro, Marjoriees_ES
dc.contributor.authorCuervo, Claudiaes_ES
dc.contributor.authorCardenas, Constanzaes_ES
dc.contributor.authorDuarte, Silviaes_ES
dc.contributor.authorDíaz, Jenny Res_ES
dc.contributor.authorThomas, María del Carmenes_ES
dc.contributor.authorLópez López, Manuel Carloses_ES
dc.contributor.authorPuerta, Concepción J.es_ES
dc.identifier.citationMemórias do Instituto Oswaldo Cruz.es_ES
dc.description.abstractTrypanosomatid type I nitroreductases (NTRs), i.e., mitochondrial enzymes that metabolise nitroaromatic pro-drugs, are essential for parasite growth, infection, and survival. Here, a type I NTR of non-virulent protozoan Trypanosoma rangeli is described and compared to those of other trypanosomatids. The NTR gene was isolated from KP1(+) and KP1(-) strains, and its corresponding transcript and 5’ untranslated region (5’UTR) were determined. Bioinformatics analyses and nitro-drug activation assays were also performed. The results indicated that the type I NTR gene is present in both KP1(-) and KP1(+) strains, with 98% identity. However, the predicted subcellular localisation of the protein differed among the strains (predicted as mitochondrial in the KP1(+) strain). Comparisons of the domains and 3D structures of the NTRs with those of orthologs demonstrated that the nitroreductase domain of T. rangeli NTR is conserved across all the strains, including the residues involved in the interaction with the FMN cofactor and in the tertiary structure characteristics of this oxidoreductase protein family. mRNA processing and expression were also observed. In addition, T. rangeli was shown to be sensitive to benznidazole and nifurtimox in a concentration-dependent manner. In summary, T. rangeli appears to have a newly discovered functional type I NTR.es_ES
dc.description.sponsorshipFinancial support: Colciencias Research (Project No. RC-595-2009), Pontificia Universidad Javeriana Research (Project No. 6728). MM and JRD were supported by the programs Jóvenes Investigadores e Innovadores 2011 and 2016 from Colciencias; MCL and MCT were supported by grants SAF2016-81003R and SAF2016-80998, respectively, from Plan Nacional I+D+i (MICINN) and RD12/0018/0021 from ISCIII-RETIC (MICINN), Spain, and FEDER.es_ES
dc.publisherInstituto Oswaldo Cruzes_ES
dc.relation.isversionofPublisher's versiones_ES
dc.subjecttype I nitroreductasees_ES
dc.subjectTrypanosoma cruzies_ES
dc.subjectTrypanosoma rangelies_ES
dc.titleIdentification of a type I nitroreductase gene in non-virulent Trypanosoma rangelies_ES
dc.description.peerreviewedPeer reviewedes_ES
oprm.item.hasRevisionno ko 0 false*
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