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
en En
| LILACS
| ID: biblio-1040572
Biblioteca responsable:
BR1.1
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
LILACS
Contexto en salud:
3_ND
Problema de salud:
3_chagas_disease
Asunto principal:
Nitrorreductasas
/
Trypanosoma rangeli
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Mem. Inst. Oswaldo Cruz
Asunto de la revista:
MEDICINA TROPICAL
/
PARASITOLOGIA
Año:
2017
Tipo del documento:
Article
País de afiliación:
Chile
/
Colombia
/
España