title: A single amino acid substitution in isozyme GST mu in Triclabendazole resistant Fasciola hepatica (Sligo strain) can substantially influence the manifestation of anthelmintic resistance.
abstract: The helminth parasite Fasciola hepatica causes fascioliasis in human and domestic ruminants. Economic losses due to this infection are estimated in U$S 2000-3000 million yearly. The most common method of control is the use of anthelmintic drugs. However, there is an increased concern about the growing appearance of F. hepatica resistance to Triclabendazole (TCBZ), an anthelmintic with activity over adult and young flukes. F. hepatica has eight Glutathione S-Transferase (GST) isozymes, which are enzymes involved in the detoxification of a wide range of substrates through chemical conjugation with glutathione. In the present work we identified and characterized the GST mu gene isolated from the TCBZ-susceptible and TCBZ-resistant F. hepatica strains. Total RNA was transcribed into cDNA by reverse transcription and a 657 bp amplicon corresponding to the GST mu gene was obtained. The comparative genetic analysis of the GST mu gene of the TCBZ susceptible strain (Cullompton) and TCBZ resistant strain (Sligo) showed three nucleotide changes and one amino acid change at position 143 in the GST mu isozyme of the TCBZ-resistant strain. These results have potential relevance as they contribute better understand the mechanisms that generate resistance to anthelmintics.
authors.affiliation: Laboratorio de Biología Celular y Molecular, Facultad de Ciencias Veterinarias, Universidad Nacional del Centro de la Provincia de Buenos Aires, 7000 Tandil, Argentina. Electronic address: vanesaf@vet.unicen.edu.ar.
authors.forename: V
authors.initials: V
authors.lastname: Fernández
authors.affiliation: Laboratorio de Inmunología, Departamento SAMP, Centro de Investigación Veterinaria de Tandil (CIVETAN-CONICET), Facultad de Ciencias Veterinarias, Universidad Nacional del Centro de la Provincia de Buenos Aires, 7000 Tandil, Argentina.
authors.forename: S
authors.initials: S
authors.lastname: Estein
authors.affiliation: Laboratorio de Inmunología, Facultad de Ciencias Veterinarias, Universidad Nacional de Cajamarca, 06001 Cajamarca, Peru.
authors.forename: P
authors.initials: P
authors.lastname: Ortiz
authors.affiliation: Laboratorio de Inmunología, Departamento SAMP, Centro de Investigación Veterinaria de Tandil (CIVETAN-CONICET), Facultad de Ciencias Veterinarias, Universidad Nacional del Centro de la Provincia de Buenos Aires, 7000 Tandil, Argentina.
authors.forename: P
authors.initials: P
authors.lastname: Luchessi
authors.affiliation: Laboratorio de Biología Celular y Molecular, Facultad de Ciencias Veterinarias, Universidad Nacional del Centro de la Provincia de Buenos Aires, 7000 Tandil, Argentina.
authors.forename: V
authors.initials: V
authors.lastname: Solana
authors.affiliation: Laboratorio de Biología Celular y Molecular, Facultad de Ciencias Veterinarias, Universidad Nacional del Centro de la Provincia de Buenos Aires, 7000 Tandil, Argentina.
authors.forename: H
authors.initials: H
authors.lastname: Solana
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000502:physiology*; D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology*; D001483:Base Sequence; D001562:Benzimidazoles / Q000494:pharmacology*; D004351:Drug Resistance; D005210:Fasciola hepatica / Q000187:drug effects* / Q000201:enzymology* / Q000235:genetics; D005982:Glutathione Transferase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D007527:Isoenzymes / Q000737:chemistry / Q000378:metabolism; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D012756:Sheep; D000077682:Triclabendazole
chemical_list: D000871:Anthelmintics; D001562:Benzimidazoles; D007527:Isoenzymes; D000077682:Triclabendazole; D005982:Glutathione Transferase
keywords: Fasciola hepatica; Glutathione S-Transferases mu; Isozyme; Triclabendazole