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

Author

Listed:
  • Young-Jun Choi

    (Washington University School of Medicine)

  • Bruce A. Rosa

    (Washington University School of Medicine)

  • Martha V. Fernandez-Baca

    (Universidad Peruana Cayetano Heredia)

  • Rodrigo A. Ore

    (Universidad Peruana Cayetano Heredia)

  • John Martin

    (Washington University School of Medicine)

  • Pedro Ortiz

    (Universidad Nacional de Cajamarca)

  • Cristian Hoban

    (Universidad Nacional de Cajamarca)

  • Miguel M. Cabada

    (Universidad Peruana Cayetano Heredia
    University of Texas Medical Branch)

  • Makedonka Mitreva

    (Washington University School of Medicine)

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.

Suggested Citation

  • Young-Jun Choi & Bruce A. Rosa & Martha V. Fernandez-Baca & Rodrigo A. Ore & John Martin & Pedro Ortiz & Cristian Hoban & Miguel M. Cabada & Makedonka Mitreva, 2025. "Independent origins and non-parallel selection signatures of triclabendazole resistance in Fasciola hepatica," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57796-5
    DOI: 10.1038/s41467-025-57796-5
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