Large scale screening for benzimidazole resistance mutations in Nematodirus battus, using both pyrosequence genotyping and deep amplicon sequencing, indicates the early emergence of resistance on UK sheep farms.


Journal

International journal for parasitology. Drugs and drug resistance
ISSN: 2211-3207
Titre abrégé: Int J Parasitol Drugs Drug Resist
Pays: Netherlands
ID NLM: 101576715

Informations de publication

Date de publication:
04 2020
Historique:
received: 09 12 2019
revised: 27 02 2020
accepted: 03 03 2020
pubmed: 7 4 2020
medline: 6 10 2020
entrez: 7 4 2020
Statut: ppublish

Résumé

Benzimidazoles (BZ) have been the anthelmintic of choice for controlling Nematodirus battus infections since their release in the 1950s. Despite heavy reliance on this single anthelmintic drug class, resistance was not identified in this nematode until 2010 (Mitchell et al., 2011). The study aimed to explore the prevalence of BZ-resistance mutations in N. battus from UK sheep flocks using deep amplicon sequencing and pyrosequencing platforms. Based on evidence from other gastrointestinal nematodes, resistance in N. battus is likely to be conferred by single nucleotide polymorphisms (SNP) within the β-tubulin isotype 1 locus at codons 167, 198 and 200. Pyrosequencing and deep amplicon sequencing assays were designed to identify the F167Y (TTC to TAC), E198A (GAA to GCA) and F200Y (TTC to TAC) SNPs. Nematodirus battus populations from 253 independent farms were analysed by pyrosequencing; 174 farm populations were included in deep amplicon sequencing and 170 were analysed using both technologies. F200Y was the most prevalent SNP identified throughout the UK, in 12-27% of the populations tested depending on assay, at a low overall individual frequency of 2.2 ± 0.6% (mean ± SEM, based on pyrosequencing results). Four out of the five populations with high frequencies (>20%) of the F200Y mutation were located in NW England. The F167Y SNP was identified, for the first time in this species, in four of the populations tested at a low frequency (1.2% ± 0.01), indicating the early emergence of the mutation. E198A or E198L were not identified in any of the isolates. Results obtained were comparable between both techniques for F200Y (Lins' CCC, r

Identifiants

pubmed: 32251964
pii: S2211-3207(20)30003-8
doi: 10.1016/j.ijpddr.2020.03.001
pmc: PMC7132121
pii:
doi:

Substances chimiques

Anthelmintics 0
Benzimidazoles 0
benzimidazole E24GX49LD8

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

68-76

Informations de copyright

Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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Auteurs

Lynsey A Melville (LA)

Department of Disease Control, Moredun Research Institute, Pentlands Science Park, Bush Loan, EH26 0PZ, UK. Electronic address: lynsey.melville@moredun.ac.uk.

Elizabeth Redman (E)

Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, CalgCary, Alberta, Canada.

Alison A Morrison (AA)

Department of Disease Control, Moredun Research Institute, Pentlands Science Park, Bush Loan, EH26 0PZ, UK.

Pai Chia Rebecca Chen (PC)

Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, CalgCary, Alberta, Canada.

Russell Avramenko (R)

Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, CalgCary, Alberta, Canada.

Sian Mitchell (S)

Centre for Preventive Medicine, Animal Health Trust, Lanwades Park, Kentford, Newmarket, Suffolk, CB8 7UU, UK.

Jan Van Dijk (J)

Zoetis, Birchwood Building, Springfield Drive, Leatherhead, KT22 7LP, UK.

Giles Innocent (G)

Biomathmatics and Statistics Scotland, JCMB, King's Buildings, Peter Guthrie Tait Road, Edinburgh, EH9 3FD, UK.

Fiona Sargison (F)

Department of Disease Control, Moredun Research Institute, Pentlands Science Park, Bush Loan, EH26 0PZ, UK.

Catriona Aitken (C)

Department of Disease Control, Moredun Research Institute, Pentlands Science Park, Bush Loan, EH26 0PZ, UK.

John S Gilleard (JS)

Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, CalgCary, Alberta, Canada.

Dave J Bartley (DJ)

Department of Disease Control, Moredun Research Institute, Pentlands Science Park, Bush Loan, EH26 0PZ, UK.

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