title: Teladorsagia circumcincta: the transcriptomic response of a multi-drug-resistant isolate to ivermectin exposure in vitro.
abstract: The emergence and spread of anthelmintic resistance in parasitic nematodes is a serious threat to the sustainability of the livestock industry. Resistance has a genetic component but the underlying mechanisms and the means by which resistant parasites survive anthelmintic treatment are still poorly understood. Differential gene expression may be implicated, especially in multi-drug resistant parasites. In this study, we investigated the transcriptomic response of a triple drug-resistant isolate of Teladorsagia circumcincta to ivermectin exposure in vitro, using Roche 454 sequencing. The study generated ∼100,000 new EST sequences, ∼50,000 each from the ivermectin-exposed and -unexposed pools of parasites. Bioinformatic analysis of the expression profiles revealed statistically significant differences in the mean expression levels of four KEGG orthologous groups, namely 'translation', 'amino acid metabolism', 'carbohydrate metabolism' and 'xenobiotic degradation and metabolism'. Notably, candidate resistance genes such as p-glycoproteins and cytochrome P450s were poorly represented in both datasets. Clusters of sequences, containing both exposed and unexposed ESTs, also revealed statistically significant differences. Four clusters were identified as cytochrome c oxidase subunits, two of these clusters had a statistically significant increase in the number of exposed ESTs compared to unexposed ESTs. Four clusters were identified as vitellogenin; three of these clusters had a statistically significant decrease in number of exposed ESTs compared to unexposed ESTs.
authors.affiliation: Moredun Research Institute, Pentlands Science Park, Bush Loan, Penicuik, Midlothian, Scotland, UK.
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Dicker
authors.forename: Mintu
authors.initials: M
authors.lastname: Nath
authors.forename: Raja
authors.initials: R
authors.lastname: Yaga
authors.forename: Alasdair J
authors.initials: AJ
authors.lastname: Nisbet
authors.forename: F Alex
authors.initials: FA
authors.lastname: Lainson
authors.forename: John S
authors.initials: JS
authors.lastname: Gilleard
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Skuce
mesh_terms: D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology*; D000977:Antiparasitic Agents / Q000494:pharmacology; D016000:Cluster Analysis; D018432:Drug Resistance, Multiple / Q000235:genetics; D020224:Expressed Sequence Tags; D005260:Female; D020869:Gene Expression Profiling; D007559:Ivermectin / Q000494:pharmacology*; D008297:Male; D018510:RNA, Helminth / Q000737:chemistry / Q000302:isolation & purification; D012756:Sheep; D014251:Trichostrongyloidea / Q000187:drug effects* / Q000235:genetics
chemical_list: D000871:Anthelmintics; D000977:Antiparasitic Agents; D018510:RNA, Helminth; D007559:Ivermectin