title: Gene expression of ABC transporters in Cooperia oncophora after field and laboratory selection with macrocyclic lactones.
abstract: The most widespread helminth parasites of grazing cattle in northern Europe are the gastrointestinal nematodes Ostertagia ostertagi and Cooperia oncophora. Heavy reliance on the use of macrocyclic lactone (ML) in cattle has led to world-wide emergence of resistance to this drug class in C. oncophora. There is evidence that members of the ATP-binding cassette (ABC) transporter family, such as P-glycoproteins (P-gp) and multidrug-resistant proteins (MRP), play a role in resistance to ML. In this study gene expression of Con-pgp9, Con-pgp11, Con-pgp12, Con-pgp16 and Con-mrp1 was examined in two isolates of C. oncophora sharing the same genetic background but exposed to ML differently. For isolate one (Laboratory-selected), adult worms were recovered before and after treatment with ML in vivo. For isolate two (Field-selected), adult worms were collected from tracer animals that had never received anthelmintics themselves. One group grazed together with untreated animals and one group grazed with animals that received suppressive prophylactic treatment with ML at monthly intervals for up to two consecutive grazing seasons. Real-time PCR data demonstrated differences in gene expression after ML selection, with the highest constitutive expression levels for Con-pgp16 and Con-mrp1. Remarkably, the same pattern of increasing expression levels of the ABC transport genes was observed in both Laboratory- and Field-selected isolates, despite the Field-selected isolate not being directly exposed to ML. The higher expression levels of ABC transporters observed in the Field-selected isolate was thus not a response to direct exposure to ML, but rather appeared to reflect a genetic characteristic inherited from worms in the previous generation which had survived exposure to ML in the co-grazing treated animals.
authors.affiliation: Department of Biomedical Sciences and Veterinary Public Health, Division of Parasitology, Swedish University of Agricultural Sciences, S-750 07 Uppsala, Sweden. Electronic address: Eva.Tyden@slu.se.
authors.forename: Eva
authors.initials: E
authors.lastname: Tydén
authors.affiliation: Department of Biomedical Sciences and Veterinary Public Health, Division of Parasitology, Swedish University of Agricultural Sciences, S-750 07 Uppsala, Sweden.
authors.forename: Moa
authors.initials: M
authors.lastname: Skarin
authors.affiliation: Department of Biomedical Sciences and Veterinary Public Health, Division of Parasitology, Swedish University of Agricultural Sciences, S-750 07 Uppsala, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Höglund
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology*; D002417:Cattle; D004351:Drug Resistance; D020869:Gene Expression Profiling; D007753:Laboratories; D007783:Lactones / Q000494:pharmacology*; D047028:Macrocyclic Compounds / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D012641:Selection, Genetic; D014251:Trichostrongyloidea / Q000187:drug effects* / Q000201:enzymology* / Q000235:genetics
chemical_list: D018528:ATP-Binding Cassette Transporters; D000871:Anthelmintics; D007783:Lactones; D047028:Macrocyclic Compounds
keywords: Cattle; Doramectin; Ivermectin; MRP; Macrocyclic lactones; P-gp; Resistant nematodes