| Author | Campos, Mônica C. O. | |
| Author | Leon, Leonor L. | |
| Author | Taylor, Martin C. | |
| Author | Kelly, John M. | |
| Access date | 2015-05-04T16:34:31Z | |
| Available date | 2015-05-04T16:34:31Z | |
| Document date | 2014 | |
| Citation | CAMPOS, MÔnica C. O. et al. Benznidazole-resistance in Trypanosoma cruzi: Evidence that distinct mechanisms can act in concert. Molecular and Biochemical Parasitology, v.193, n.1, p.17-19, 2014. | pt_BR |
| ISSN | 0166-6851 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/10161 | |
| Language | eng | pt_BR |
| Publisher | Elsevier | pt_BR |
| Rights | open access | |
| Subject in Portuguese | Trypanosoma cruzi | pt_BR |
| Subject in Portuguese | Doença de Chagas | pt_BR |
| Subject in Portuguese | Resistência a Medicamentos | pt_BR |
| Title | Benznidazole-resistance in Trypanosoma cruzi: Evidence that distinct mechanisms can act in concert | pt_BR |
| Type | Article | |
| DOI | 10.1016/j.molbiopara.2014.01.002 | pt_BR |
| Abstract | Benznidazole is the main drug used to treat Trypanosoma cruzi infections. However, frequent instances
of treatment failure have been reported. To better understand potential resistance mechanisms, we analysed
three clones isolated from a single parasite population that had undergone benznidazole-selection.
These clones exhibited differing levels of benznidazole-resistance (varying between 9 and 26-fold), and
displayed cross-resistance to nifurtimox (2 to 4-fold). Each clone had acquired a stop-codon-generating
mutation in the gene which encodes the nitroreductase (TcNTR) that is responsible for activating nitroheterocyclic
pro-drugs. In addition, one clone had lost a copy of the chromosome containing TcNTR.
However, these processes alone are insufficient to account for the extent and diversity of benznidazoleresistance.
It is implicit from our results that additional mechanisms must also operate and that T. cruzi
has an intrinsic ability to develop drug-resistance by independent sequential steps, even within a single
population. This has important implications for drug development strategies. | pt_BR |
| Affilliation | London School of Hygiene and Tropical Medicine. Department of Pathogen Molecular Biology. London, UK / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanosomatídeos. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanosomatídeos. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | London School of Hygiene and Tropical Medicine. Department of Pathogen Molecular Biology. London, UK. | pt_BR |
| Affilliation | London School of Hygiene and Tropical Medicine. Department of Pathogen Molecular Biology. London, UK. | pt_BR |
| Subject | Trypanosoma cruzi | pt_BR |
| Subject | Drug resistance | pt_BR |
| Subject | Benznidazole | pt_BR |
| Subject | Nitroreductase | pt_BR |
| Subject in Spanish | Trypanosoma cruzi | pt_BR |
| Subject in Spanish | Resistencia a Medicamentos | pt_BR |
| Subject in Spanish | Enfermedad de Chagas | pt_BR |
| xmlui.metadata.dc.subject.ods | 03 Saúde e Bem-Estar | |
