Pleiotropic alterations in gene expression in Latin American Fasciola hepatica isolates with different susceptibility to drugs
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2018 |
| Outros Autores: | , , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/28976 |
Resumo: | Departamento de Genética. Facultad de Medicina. Universidad de la Republica. Montevideo, Uruguay/Instituto de Investigaciones Biológicas Clemente 28 Estable. MEC, Montevideo, Uruguay |
| id |
CRUZ_bedc74ed1c268e16ddb0128e437af3ab |
|---|---|
| oai_identifier_str |
oai:www.arca.fiocruz.br:icict/28976 |
| network_acronym_str |
CRUZ |
| network_name_str |
Repositório Institucional da FIOCRUZ (ARCA) |
| repository_id_str |
2135 |
| spelling |
Radio, SantiagoFontenla, SantiagoSolana, VictoriaSalim, Anna Carolina MatosAraújo, Flávio Marcos GomesOrtiz, PedroHoban, CristianMiranda, EstefanGayo, ValeriaPais, Fabiano Sviatopolk MirskySolana, HugoOliveira, Guilherme Correa deSmircich, PabloTort, José F.2018-09-21T18:55:58Z2018-09-21T18:55:58Z2018RADIO, 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, 2018.1756-3305https://www.arca.fiocruz.br/handle/icict/2897610.1186/s13071-017-2553-2engBioMed Centralalbendazolresistencia a drogasFascola hepaticaTranscriptômicaTriclabendazolAlbendazoleAmerican isolatesDrug resistanceFascola hepaticaTranscriptomicsTriclabendazolePleiotropic alterations in gene expression in Latin American Fasciola hepatica isolates with different susceptibility to drugsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleDepartamento de Genética. Facultad de Medicina. Universidad de la Republica. Montevideo, Uruguay/Instituto de Investigaciones Biológicas Clemente 28 Estable. MEC, Montevideo, UruguayDepartamento de Genética. Facultad de Medicina. Universidad de la Republica. Montevideo, UruguayLaboratorio de Biología Celular y Molecular. Facultad de Ciencias Veterinarias. Universidad Nacional del Centro de la Provincia de Buenos Aires. Tandil, ArgentinaFundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, BrazilFundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, BrazilLaboratorio de Inmunología. Facultad de Ciencias Veterinarias. Universidad Nacional de Cajamarca. Cajamarca, PeruLaboratorio de Inmunología. Facultad de Ciencias Veterinarias. Universidad Nacional de Cajamarca. Cajamarca, PeruInstituto Nacional de Investigaciones Forestales. Agrícolas y Pecuarias.Secretaria de Agricultura, Ganadería, Desarrollo Rural, Pesca y Alimentación. Morelos, MexicoDepartamento de Parasitología. División de Laboratorios Veterinarios “Miguel C. Rubino”. Ministerio de Ganadería, Agricultura y Pesca. Montevideo, UruguayFundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, BrazilLaboratorio de Biología Celular y Molecular. Facultad de Ciencias Veterinarias. Universidad Nacional del Centro de la Provincia de Buenos Aires. Tandil, ArgentinaFundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil/Instituto Tecnológico Vale. Belém, PA, BrazilDepartamento 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, UruguayDepartamento de Genética. Facultad de Medicina. Universidad de la Republica. Montevideo, UruguayBACKGROUND: 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.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-83082https://www.arca.fiocruz.br/bitstream/icict/28976/1/license.txt9193a7c197bc67acd023525e72a03240MD51ORIGINALPleiotropic alterations.pdfPleiotropic alterations.pdfapplication/pdf12637639https://www.arca.fiocruz.br/bitstream/icict/28976/2/Pleiotropic%20alterations.pdff2de77373e826abb2f078bca8c8d80dfMD52TEXTPleiotropic alterations.pdf.txtPleiotropic alterations.pdf.txtExtracted texttext/plain860https://www.arca.fiocruz.br/bitstream/icict/28976/3/Pleiotropic%20alterations.pdf.txtce5f948054e398edcc06c26d4e219854MD53icict/289762019-06-19 10:07:03.458oai:www.arca.fiocruz.br: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Repositório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352019-06-19T13:07:03Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false |
| dc.title.pt_BR.fl_str_mv |
Pleiotropic alterations in gene expression in Latin American Fasciola hepatica isolates with different susceptibility to drugs |
| title |
Pleiotropic alterations in gene expression in Latin American Fasciola hepatica isolates with different susceptibility to drugs |
| spellingShingle |
Pleiotropic alterations in gene expression in Latin American Fasciola hepatica isolates with different susceptibility to drugs Radio, Santiago albendazol resistencia a drogas Fascola hepatica Transcriptômica Triclabendazol Albendazole American isolates Drug resistance Fascola hepatica Transcriptomics Triclabendazole |
| title_short |
Pleiotropic alterations in gene expression in Latin American Fasciola hepatica isolates with different susceptibility to drugs |
| title_full |
Pleiotropic alterations in gene expression in Latin American Fasciola hepatica isolates with different susceptibility to drugs |
| title_fullStr |
Pleiotropic alterations in gene expression in Latin American Fasciola hepatica isolates with different susceptibility to drugs |
| title_full_unstemmed |
Pleiotropic alterations in gene expression in Latin American Fasciola hepatica isolates with different susceptibility to drugs |
| title_sort |
Pleiotropic alterations in gene expression in Latin American Fasciola hepatica isolates with different susceptibility to drugs |
| author |
Radio, Santiago |
| author_facet |
Radio, Santiago Fontenla, Santiago Solana, Victoria Salim, Anna Carolina Matos Araújo, Flávio Marcos Gomes Ortiz, Pedro Hoban, Cristian Miranda, Estefan Gayo, Valeria Pais, Fabiano Sviatopolk Mirsky Solana, Hugo Oliveira, Guilherme Correa de Smircich, Pablo Tort, José F. |
| author_role |
author |
| author2 |
Fontenla, Santiago Solana, Victoria Salim, Anna Carolina Matos Araújo, Flávio Marcos Gomes Ortiz, Pedro Hoban, Cristian Miranda, Estefan Gayo, Valeria Pais, Fabiano Sviatopolk Mirsky Solana, Hugo Oliveira, Guilherme Correa de Smircich, Pablo Tort, José F. |
| author2_role |
author author author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Radio, Santiago Fontenla, Santiago Solana, Victoria Salim, Anna Carolina Matos Araújo, Flávio Marcos Gomes Ortiz, Pedro Hoban, Cristian Miranda, Estefan Gayo, Valeria Pais, Fabiano Sviatopolk Mirsky Solana, Hugo Oliveira, Guilherme Correa de Smircich, Pablo Tort, José F. |
| dc.subject.other.pt_BR.fl_str_mv |
albendazol resistencia a drogas Fascola hepatica Transcriptômica Triclabendazol |
| topic |
albendazol resistencia a drogas Fascola hepatica Transcriptômica Triclabendazol Albendazole American isolates Drug resistance Fascola hepatica Transcriptomics Triclabendazole |
| dc.subject.en.pt_BR.fl_str_mv |
Albendazole American isolates Drug resistance Fascola hepatica Transcriptomics Triclabendazole |
| description |
Departamento de Genética. Facultad de Medicina. Universidad de la Republica. Montevideo, Uruguay/Instituto de Investigaciones Biológicas Clemente 28 Estable. MEC, Montevideo, Uruguay |
| publishDate |
2018 |
| dc.date.accessioned.fl_str_mv |
2018-09-21T18:55:58Z |
| dc.date.available.fl_str_mv |
2018-09-21T18:55:58Z |
| dc.date.issued.fl_str_mv |
2018 |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
| dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.citation.fl_str_mv |
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. |
| dc.identifier.uri.fl_str_mv |
https://www.arca.fiocruz.br/handle/icict/28976 |
| dc.identifier.issn.pt_BR.fl_str_mv |
1756-3305 |
| dc.identifier.doi.none.fl_str_mv |
10.1186/s13071-017-2553-2 |
| identifier_str_mv |
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. 1756-3305 10.1186/s13071-017-2553-2 |
| url |
https://www.arca.fiocruz.br/handle/icict/28976 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
| eu_rights_str_mv |
openAccess |
| dc.publisher.none.fl_str_mv |
BioMed Central |
| publisher.none.fl_str_mv |
BioMed Central |
| dc.source.none.fl_str_mv |
reponame:Repositório Institucional da FIOCRUZ (ARCA) instname:Fundação Oswaldo Cruz (FIOCRUZ) instacron:FIOCRUZ |
| instname_str |
Fundação Oswaldo Cruz (FIOCRUZ) |
| instacron_str |
FIOCRUZ |
| institution |
FIOCRUZ |
| reponame_str |
Repositório Institucional da FIOCRUZ (ARCA) |
| collection |
Repositório Institucional da FIOCRUZ (ARCA) |
| bitstream.url.fl_str_mv |
https://www.arca.fiocruz.br/bitstream/icict/28976/1/license.txt https://www.arca.fiocruz.br/bitstream/icict/28976/2/Pleiotropic%20alterations.pdf https://www.arca.fiocruz.br/bitstream/icict/28976/3/Pleiotropic%20alterations.pdf.txt |
| bitstream.checksum.fl_str_mv |
9193a7c197bc67acd023525e72a03240 f2de77373e826abb2f078bca8c8d80df ce5f948054e398edcc06c26d4e219854 |
| bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 |
| repository.name.fl_str_mv |
Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ) |
| repository.mail.fl_str_mv |
repositorio.arca@fiocruz.br |
| _version_ |
1798324762583236608 |