Identification of a type I nitroreductase gene in non-virulent Trypanosoma rangeli
Mem. Inst. Oswaldo Cruz
;
112(7): 504-509, July 2017. tab, graf
Article
Dans Anglais
| LILACS
| ID: biblio-1040572
ABSTRACT
ABSTRACT Trypanosomatid 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.
Texte intégral:
Disponible
Indice:
LILAS (Amériques)
Sujet Principal:
Nitroréductases
/
Trypanosoma rangeli
Type d'étude:
Etude diagnostique
/
Étude pronostique
Limites du sujet:
Humains
langue:
Anglais
Texte intégral:
Mem. Inst. Oswaldo Cruz
Thème du journal:
Médecine tropicale
/
Parasitologie
Année:
2017
Type:
Article
Pays d'affiliation:
Chili
/
Colombie
/
Espagne
Institution/Pays d'affiliation:
Consejo Superior de Investigaciones Científicas/ES
/
Pontificia Universidad Católica de Valparaíso/CL
/
Pontificia Universidad Javeriana/CO
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