P-glycoprotein-9 and macrocyclic lactone resistance status in selected strains of the ovine gastrointestinal nematode, Teladorsagia circumcincta

Turnbull, F. , Jonsson, N. , Kenyon, F., Skuce, P. J. and Bisset, S. A. (2018) P-glycoprotein-9 and macrocyclic lactone resistance status in selected strains of the ovine gastrointestinal nematode, Teladorsagia circumcincta. International Journal for Parasitology: Drugs and Drug Resistance, 8(1), pp. 70-80. (doi:10.1016/j.ijpddr.2018.01.004) (PMID:29414109)

Turnbull, F. , Jonsson, N. , Kenyon, F., Skuce, P. J. and Bisset, S. A. (2018) P-glycoprotein-9 and macrocyclic lactone resistance status in selected strains of the ovine gastrointestinal nematode, Teladorsagia circumcincta. International Journal for Parasitology: Drugs and Drug Resistance, 8(1), pp. 70-80. (doi:10.1016/j.ijpddr.2018.01.004) (PMID:29414109)

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Abstract

The Teladorsagia circumcincta P-glycoprotein-9 (Tci-pgp-9) gene has previously been implicated in multiple-anthelmintic resistance in this parasite. Here we further characterise genetic diversity in Tci-pgp-9 and its possible role in ivermectin (IVM) and multi-drug resistance using two UK field isolates of T. circumcincta, one susceptible to anthelmintics (MTci2) and the other resistant to most available anthelmintics including IVM (MTci5). A comparison of full-length Tci-pgp-9 cDNA transcripts from the MTci2 and MTci5 isolates (∼3.8 kb in both cases) indicated that they shared 95.6% and 99.5% identity at the nucleotide and amino acid levels, respectively. Nine non-synonymous SNPs were found in the MTci5 sequences relative to their MTci2 counterparts. Twelve genomic sequence variants of the first internucleotide binding domain of Tci-pgp-9 were identified and up to 10 of these were present in some individual worms, strongly supporting previous evidence that amplification of this gene has occurred in T. circumcincta. On average, fewer distinct sequence variants of Tci-pgp-9 were present in individual worms of the MTci5 isolate than in those of the MTci2 isolate. A further reduction in the number of sequence variants was observed in individuals derived from an IVM-treated sub-population of MTci5. These findings suggest that Tci-pgp-9 was under purifying selection in the face of IVM treatment in T. circumcincta, with some sequence variants being selected against.

Item Type:Articles
Additional Information:This work was funded by Moredun Research Institute (UK) and AgResearch (NZ)
Keywords:Anthelmintic resistance, Ivermectin, P-glycoprotein, Teladorsagia circumcincta
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Jonsson, Professor Nicholas and Turnbull, Dr Frank
Authors: Turnbull, F., Jonsson, N., Kenyon, F., Skuce, P. J., and Bisset, S. A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Biodiversity Animal Health and Comparative Medicine
Journal Name:International Journal for Parasitology: Drugs and Drug Resistance
Publisher:Elsevier
ISSN:2211-3207
ISSN (Online):2211-3207
Published Online:31 January 2018
Copyright Holders:Copyright © 2018 Elsevier on behalf of Australian Society for Parasitology
First Published:First published in International Journal for Parasitology: Drugs and Drug Resistance 8(1):70-80
Publisher Policy:Reproduced under a Creative Commons License

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