title: The T687G SNP in a P-glycoprotein gene of Fasciola hepatica is not associated with resistance to triclabendazole in two resistant Australian populations.
abstract: Triclabendazole (TCBZ) is widely used for control of Fasciola hepatica (liver fluke) in animals and humans and resistance to this drug is now widespread. However, the mechanism of resistance to TCBZ is not known. A T687G single nucleotide polymorphism (SNP) in a P-glycoprotein gene was proposed as a molecular marker for TCBZ resistance in F. hepatica (Wilkinson et al., 2012). We analyzed this Pgp gene from TCBZ-susceptible and TCBZ-resistant populations from Australia to determine if the SNP was a marker for TCBZ resistance. From the 21 parasites studied we observed 27 individual haplotypes in the Pgp sequences which comprised seven haplotypic groups (A-G), with haplotypes A and B representing 81% of the total observed. The T687G SNP was not observed in either of the resistant or susceptible populations. We conclude that the T687G SNP in this Pgp gene is not associated with TCBZ resistance in these Australian F. hepatica populations and therefore unlikely to be a universal molecular marker for TCBZ resistance.
authors.affiliation: Department of Agricultural Sciences, Centre for AgriBioscience, La Trobe University, Bundoora 3083, Victoria, Australia.
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Elliott
authors.affiliation: Department of Agricultural Sciences, Centre for AgriBioscience, La Trobe University, Bundoora 3083, Victoria, Australia. Electronic address: t.spithill@latrobe.edu.au.
authors.forename: Terry W
authors.initials: TW
authors.lastname: Spithill
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology*; D001315:Australia; D001483:Base Sequence; D001562:Benzimidazoles / Q000494:pharmacology*; D004351:Drug Resistance; D005210:Fasciola hepatica / Q000187:drug effects* / Q000235:genetics*; D005211:Fascioliasis / Q000469:parasitology*; D015801:Helminth Proteins / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide; D000077682:Triclabendazole
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000871:Anthelmintics; D001562:Benzimidazoles; D015801:Helminth Proteins; D000077682:Triclabendazole
keywords: Drug resistance; Fasciola hepatica; P-glycoprotein; SNP; Triclabendazole