PMID- 28591312 OWN - NLM STAT- MEDLINE DCOM- 20170824 LR - 20181113 IS - 1678-8060 (Electronic) IS - 0074-0276 (Print) IS - 0074-0276 (Linking) VI - 112 IP - 7 DP - 2017 Jul TI - Identification of a type I nitroreductase gene in non-virulent Trypanosoma rangeli. PG - 504-509 LID - S0074-02762017000700504 [pii] LID - 10.1590/0074-02760160532 [doi] AB - 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. FAU - Montenegro, Marjorie AU - Montenegro M AD - Pontificia Universidad Javeriana, Facultad de Ciencias, Departamento de Microbiologia, Laboratorio de Parasitologia Molecular, Bogota, Colombia. AD - Consejo Superior de Investigaciones Cientificas, Instituto de Parasitologia y Biomedicina Lopez Neyra, Granada, Spain. FAU - Cuervo, Claudia AU - Cuervo C AD - Pontificia Universidad Javeriana, Facultad de Ciencias, Departamento de Microbiologia, Laboratorio de Parasitologia Molecular, Bogota, Colombia. FAU - Cardenas, Constanza AU - Cardenas C AD - Pontificia Universidad Catolica de Valparaiso, Nucleo de Biotecnologia Curauma, Valparaiso, Chile. FAU - Duarte, Silvia AU - Duarte S AD - Pontificia Universidad Javeriana, Facultad de Ciencias, Departamento de Microbiologia, Laboratorio de Parasitologia Molecular, Bogota, Colombia. FAU - Diaz, Jenny R AU - Diaz JR AD - Pontificia Universidad Javeriana, Facultad de Ciencias, Departamento de Microbiologia, Laboratorio de Parasitologia Molecular, Bogota, Colombia. FAU - Thomas, M Carmen AU - Thomas MC AD - Consejo Superior de Investigaciones Cientificas, Instituto de Parasitologia y Biomedicina Lopez Neyra, Granada, Spain. FAU - Lopez, Manuel C AU - Lopez MC AD - Consejo Superior de Investigaciones Cientificas, Instituto de Parasitologia y Biomedicina Lopez Neyra, Granada, Spain. FAU - Puerta, Concepcion J AU - Puerta CJ AD - Pontificia Universidad Javeriana, Facultad de Ciencias, Departamento de Microbiologia, Laboratorio de Parasitologia Molecular, Bogota, Colombia. LA - eng PT - Journal Article PL - Brazil TA - Mem Inst Oswaldo Cruz JT - Memorias do Instituto Oswaldo Cruz JID - 7502619 RN - 0 (DNA, Protozoan) RN - EC 1.- (aromatic NADH-dependent nitroreductase) RN - EC 1.7.- (Nitroreductases) SB - IM MH - Base Sequence MH - DNA, Protozoan/genetics MH - Genetic Variation/genetics MH - Humans MH - Nitroreductases/*genetics MH - Sequence Analysis, DNA MH - Trypanosoma rangeli/*enzymology/genetics PMC - PMC5452488 EDAT- 2017/06/08 06:00 MHDA- 2017/08/25 06:00 PMCR- 2017/07/01 CRDT- 2017/06/08 06:00 PHST- 2016/12/12 00:00 [received] PHST- 2017/03/22 00:00 [accepted] PHST- 2017/07/01 00:00 [pmc-release] PHST- 2017/06/08 06:00 [entrez] PHST- 2017/06/08 06:00 [pubmed] PHST- 2017/08/25 06:00 [medline] AID - S0074-02762017000700504 [pii] AID - 0074-02760160532 [pii] AID - 10.1590/0074-02760160532 [doi] PST - ppublish SO - Mem Inst Oswaldo Cruz. 2017 Jul;112(7):504-509. doi: 10.1590/0074-02760160532.