Author | Radio, Santiago | |
Author | Fontenla, Santiago | |
Author | Solana, Victoria | |
Author | Salim, Anna Carolina Matos | |
Author | Araújo, Flávio Marcos Gomes | |
Author | Ortiz, Pedro | |
Author | Hoban, Cristian | |
Author | Miranda, Estefan | |
Author | Gayo, Valeria | |
Author | Pais, Fabiano Sviatopolk Mirsky | |
Author | Solana, Hugo | |
Author | Oliveira, Guilherme Correa de | |
Author | Smircich, Pablo | |
Author | Tort, José F. | |
Access date | 2018-09-21T18:55:58Z | |
Available date | 2018-09-21T18:55:58Z | |
Document date | 2018 | |
Citation | RADIO, Santiago et al. Pleiotropic alterations in gene expression in Latin American Fasciola hepatica isolates with different susceptibility to drugs. Parasit Vectors ,v. 11, n. 1, 56, 2018. | pt_BR |
ISSN | 1756-3305 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/28976 | |
Language | eng | pt_BR |
Publisher | BioMed Central | pt_BR |
Rights | open access | pt_BR |
Subject in Portuguese | albendazol | pt_BR |
Subject in Portuguese | resistencia a drogas | pt_BR |
Subject in Portuguese | Fascola hepatica | pt_BR |
Subject in Portuguese | Transcriptômica | pt_BR |
Subject in Portuguese | Triclabendazol | pt_BR |
Title | Pleiotropic alterations in gene expression in Latin American Fasciola hepatica isolates with different susceptibility to drugs | pt_BR |
Type | Article | pt_BR |
DOI | 10.1186/s13071-017-2553-2 | |
Abstract | BACKGROUND: Fasciola hepatica is the main agent of fasciolosis, a zoonotic disease affecting livestock worldwide, and an emerging food-borne disease in humans. Even when effective treatments are available, drugs are costly and can result in tolerance, liver damage and normally they do not prevent reinfection. Drug-resistant strains in livestock have been reported in various countries and, more worryingly, drug resistance in human cases has emerged in South America. The present study aims to characterize the transcriptome of two South American resistant isolates, the Cajamarca isolate from Peru, resistant to both triclabendazole and albendazole (TCBZR/ABZR) and the Rubino isolate from Uruguay, resistant to ABZ (TCBZS/ABZR), and compare them to a sensitive strain (Cenapa, Mexico, TCBZS/ABZS) to reveal putative molecular mechanisms leading to drug resistance.
RESULTS: We observed a major reduction in transcription in the Cajamarca TCBZR/ABZR isolate in comparison to the other isolates. While most of the differentially expressed genes are still unannotated, several trends could be detected. Specific reduction in the expression levels of cytoskeleton proteins was consistent with a role of tubulins as putative targets of triclabendazole (TCBZ). A marked reduction of adenylate cyclase might be underlying pleiotropic effects on diverse metabolic pathways of the parasite. Upregulation of GST mu isoforms suggests this detoxifying mechanism as one of the strategies associated with resistance.
CONCLUSIONS: Our results stress the value of transcriptomic approaches as a means of providing novel insights to advance the understanding of drug mode of action and drug resistance. The results provide evidence for pleiotropic variations in drug-resistant isolates consistent with early observations of TCBZ and ABZ effects and recent proteomic findings. | pt_BR |
Affilliation | Departamento de Genética. Facultad de Medicina. Universidad de la Republica. Montevideo, Uruguay/Instituto de Investigaciones Biológicas Clemente 28 Estable. MEC, Montevideo, Uruguay | pt_BR |
Affilliation | Departamento de Genética. Facultad de Medicina. Universidad de la Republica. Montevideo, Uruguay | pt_BR |
Affilliation | Laboratorio de Biología Celular y Molecular. Facultad de Ciencias Veterinarias. Universidad Nacional del Centro de la Provincia de Buenos Aires. Tandil, Argentina | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil | pt_BR |
Affilliation | Laboratorio de Inmunología. Facultad de Ciencias Veterinarias. Universidad Nacional de Cajamarca. Cajamarca, Peru | pt_BR |
Affilliation | Laboratorio de Inmunología. Facultad de Ciencias Veterinarias. Universidad Nacional de Cajamarca. Cajamarca, Peru | pt_BR |
Affilliation | Instituto Nacional de Investigaciones Forestales. Agrícolas y Pecuarias.Secretaria de Agricultura, Ganadería, Desarrollo Rural, Pesca y Alimentación. Morelos, Mexico | pt_BR |
Affilliation | Departamento de Parasitología. División de Laboratorios Veterinarios “Miguel C. Rubino”. Ministerio de Ganadería, Agricultura y Pesca. Montevideo, Uruguay | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil | pt_BR |
Affilliation | Laboratorio de Biología Celular y Molecular. Facultad de Ciencias Veterinarias. Universidad Nacional del Centro de la Provincia de Buenos Aires. Tandil, Argentina | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil/Instituto Tecnológico Vale. Belém, PA, Brazil | pt_BR |
Affilliation | Departamento de Genética. Facultad de Medicina. Universidad de la Republica. Montevideo, Uruguay/Instituto de Investigaciones Biológicas Clemente 28 Estable. MEC, Montevideo, Uruguay/Laboratorio de Interacciones Moleculares. Facultad de Ciencias. Universidad de la Republica. Montevideo, Uruguay | pt_BR |
Affilliation | Departamento de Genética. Facultad de Medicina. Universidad de la Republica. Montevideo, Uruguay | pt_BR |
Subject | Albendazole | pt_BR |
Subject | American isolates | pt_BR |
Subject | Drug resistance | pt_BR |
Subject | Fascola hepatica | pt_BR |
Subject | Transcriptomics | pt_BR |
Subject | Triclabendazole | pt_BR |