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

Young Jun Choi; Bruce A. Rosa; Martha V. Fernandez-Baca; Rodrigo A. Ore; John Martin; Pedro Ortiz; Cristian Hoban; Miguel M. Cabada; Makedonka Mitreva

doi:10.1038/s41467-025-57796-5

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

Young Jun Choi, Bruce A. Rosa, Martha V. Fernandez-Baca, Rodrigo A. Ore, John Martin, Pedro Ortiz, Cristian Hoban, Miguel M. Cabada, Makedonka Mitreva

Internal Medicine

Research output: Contribution to journal › Article › peer-review

Abstract

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 (F_ST 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.

Original language	English (US)
Article number	2996
Journal	Nature communications
Volume	16
Issue number	1
DOIs	https://doi.org/10.1038/s41467-025-57796-5
State	Published - Dec 2025

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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title = "Independent origins and non-parallel selection signatures of triclabendazole resistance in Fasciola hepatica",

abstract = "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.",

author = "Choi, {Young Jun} and Rosa, {Bruce A.} and Fernandez-Baca, {Martha V.} and Ore, {Rodrigo A.} and John Martin and Pedro Ortiz and Cristian Hoban and Cabada, {Miguel M.} and Makedonka Mitreva",

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AU - Choi, Young Jun

AU - Rosa, Bruce A.

AU - Fernandez-Baca, Martha V.

AU - Ore, Rodrigo A.

AU - Martin, John

AU - Ortiz, Pedro

AU - Hoban, Cristian

AU - Cabada, Miguel M.

AU - Mitreva, Makedonka

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

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