Bile salt-mediated activation of a type-1 nuclear receptor of Fasciola gigantica (FgNR1)
Issued Date
2026-07-01
Resource Type
ISSN
03044017
eISSN
18732550
Scopus ID
2-s2.0-105038838403
Journal Title
Veterinary Parasitology
Volume
345
Rights Holder(s)
SCOPUS
Bibliographic Citation
Veterinary Parasitology Vol.345 (2026)
Suggested Citation
Kankul K., Chaimon S., Prathaphan P., Tanramluk D., Sanannam B., Thongsepee N., Sangpairoj K., Phannasil P., Phasai S., Adisakwattana P., Chantree P., Martviset P. Bile salt-mediated activation of a type-1 nuclear receptor of Fasciola gigantica (FgNR1). Veterinary Parasitology Vol.345 (2026). doi:10.1016/j.vetpar.2026.110800 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/116838
Title
Bile salt-mediated activation of a type-1 nuclear receptor of Fasciola gigantica (FgNR1)
Corresponding Author(s)
Other Contributor(s)
Abstract
Fasciolosis, caused by Fasciola hepatica and Fasciola gigantica, is a major parasitic disease of livestock and humans. The increasing reports of drug resistance emphasize the need for novel therapeutic targets. However, before identifying a drug target, the parasite's biological processes need to be understood. F. gigantica, the predominant species in Asia, inhabits the bile duct, suggesting adaptation to bile-rich environments. We previously reported the discovery of a type-1 nuclear receptor from F. gigantica (FgNR1). We hypothesized that it functions as a bile salt–responsive transcription factor essential for parasite biology, but the exact functions have never been reported. Sequence analysis revealed that the ligand-binding domain (LBD) of FgNR1 (FgNR1-LBD) contains a conserved nuclear receptor signature motif (Tτ) and shares high homology with bile salt–responsive nuclear receptors in mammals, indicating conserved ligand recognition mechanisms. Using a luciferase reporter assay in a double-stable mammalian cell system, we demonstrate that the bile salts taurocholic acid (TCA) and glycocholic acid (GCA) significantly activate FgNR1-LBD–dependent transcriptional activity. Consistently, molecular docking analyses showed strong binding affinities of these bile salts within the predicted ligand-binding pocket of FgNR1-LBD. These findings provide the first functional evidence for bile salt regulation of gene expression via FgNR1. Importantly, this study establishes FgNR1-LBD as a tractable, parasite-specific molecular target, providing a foundation for understanding host-parasite interactions and furthering the discovery of agonists, antagonists, or inhibitors to disrupt parasite biological processes.