Teladorsagia circumcincta

the transcriptomic response of a multi-drug-resistant isolate to ivermectin exposure in vitro

Alison J Dicker, Mintu Nath, Raja Yaga, Alasdair J Nisbet, F Alex Lainson, John S Gilleard, Philip J Skuce (Corresponding Author)

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)351-356
Number of pages6
JournalExperimental Parasitology
Volume127
Issue number2
Early online date3 Sep 2010
DOIs
Publication statusPublished - Feb 2011

Fingerprint

Ivermectin
Expressed Sequence Tags
Pharmaceutical Preparations
Parasites
Anthelmintics
Vitellogenins
Carbohydrate Metabolism
Livestock
Xenobiotics
Electron Transport Complex IV
Cytochromes
Computational Biology
In Vitro Techniques
Glycoproteins
Industry
Gene Expression
Amino Acids
Genes

Keywords

  • Animals
  • Anthelmintics/pharmacology
  • Antiparasitic Agents/pharmacology
  • Cluster Analysis
  • Drug Resistance, Multiple/genetics
  • Expressed Sequence Tags
  • Female
  • Gene Expression Profiling
  • Ivermectin/pharmacology
  • Male
  • RNA, Helminth/chemistry
  • Sheep
  • Trichostrongyloidea/drug effects

Cite this

Teladorsagia circumcincta : the transcriptomic response of a multi-drug-resistant isolate to ivermectin exposure in vitro. / Dicker, Alison J; Nath, Mintu; Yaga, Raja; Nisbet, Alasdair J; Lainson, F Alex; Gilleard, John S; Skuce, Philip J (Corresponding Author).

In: Experimental Parasitology, Vol. 127, No. 2, 02.2011, p. 351-356.

Research output: Contribution to journalArticle

Dicker, Alison J ; Nath, Mintu ; Yaga, Raja ; Nisbet, Alasdair J ; Lainson, F Alex ; Gilleard, John S ; Skuce, Philip J. / Teladorsagia circumcincta : the transcriptomic response of a multi-drug-resistant isolate to ivermectin exposure in vitro. In: Experimental Parasitology. 2011 ; Vol. 127, No. 2. pp. 351-356.
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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.",
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AB - 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.

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