Pleiotropic alterations in gene expression in Latin American Fasciola hepatica isolates with different susceptibility to drugs

dc.creatorRadio, Santiago
dc.creatorFontenla, Santiago
dc.creatorSolana, Victoria
dc.creatorSalim, Anna Carolina Matos
dc.creatorAraújo, Flávio Marcos Gomes
dc.creatorOrtiz, Pedro
dc.creatorHoban, Cristian
dc.creatorMiranda, Estefan
dc.creatorGayo, Valeria
dc.creatorPais, Fabiano Sviatopolk Mirsky
dc.creatorSolana, Hugo
dc.creatorOliveira, Guilherme Correa de
dc.creatorSmircich, Pablo
dc.creatorTort, José F.
dc.date2018-09-21T18:55:58Z
dc.date2018-09-21T18:55:58Z
dc.date2018
dc.date.accessioned2023-09-26T20:47:29Z
dc.date.available2023-09-26T20:47:29Z
dc.identifierRADIO, 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.identifier1756-3305
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/28976
dc.identifier10.1186/s13071-017-2553-2
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8863957
dc.descriptionBACKGROUND: 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.
dc.formatapplication/pdf
dc.languageeng
dc.publisherBioMed Central
dc.rightsopen access
dc.subjectalbendazol
dc.subjectresistencia a drogas
dc.subjectFascola hepatica
dc.subjectTranscriptômica
dc.subjectTriclabendazol
dc.subjectAlbendazole
dc.subjectAmerican isolates
dc.subjectDrug resistance
dc.subjectFascola hepatica
dc.subjectTranscriptomics
dc.subjectTriclabendazole
dc.titlePleiotropic alterations in gene expression in Latin American Fasciola hepatica isolates with different susceptibility to drugs
dc.typeArticle


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