Independent origins and non-parallel selection signatures of triclabendazole resistance in Fasciola hepatica.

• Autores: Choi, Y.-J., Rosa, B.A., Fernandez-Baca, M.V., Ore, R.A., Martin, J., Ortiz-Oblitas, P., Hobán-Vergara, C., Cabada, M.M., Mitreva, M.
• Formato: artículo
• Fecha de Publicación: 2025
• Institución: Universidad Nacional de Cajamarca
• Repositorio: UNC-Institucional
• Lenguaje: inglés
• OAI Identifier: oai:repositorio.unc.edu.pe:20.500.14074/9803
• Enlace del recurso: http://hdl.handle.net/20.500.14074/9803; https://doi.org/10.1038/s41467-025-57796-5
• Nivel de acceso: acceso abierto
• Materia: triclabendazole; Fasciola hepatica; https://purl.org/pe-repo/ocde/ford#3.03.07

Triclabendazole (TCBZ) is the primary treatment for fascioliasis, a global foodborne zoonosis caused by Fasciola hepatica. Widespread resistance to TCBZ (TCBZ-R) in livestock and a rapid rise in resistant human infections are significant concerns. To understand the genetic basis of TCBZ-R, we sequenced the genomes of 99 TCBZ-sensitive (TCBZ-S) and 210 TCBZ-R adult flukes from 146 bovine livers in Cusco, Peru. We identify genomic regions of high differentiation (FST outliers above the 99.9th percentile) that encod genes involved in the EGFR-PI3K-mTOR-S6K pathway and microtubule function. Transcript expression differences are observed in microtubule-related genes between TCBZ-S and -R flukes, both without drug treatment and in response to treatment. Using only 30 SNPs, it is possible to differentiate between TCBZ-S and -R parasites with ≥75% accuracy. Our outlier loci are distinct from the previously reported TCBZ-R-associated QTLs in the UK, suggesting an independent evolution of resistance alleles. Effective genetics-based TCBZ-R surveillance must consider the heterogeneity of loci under selection across diverse geographical populations.