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在后基因组时代评估驱虫药耐药性风险:一项概念验证研究评估了在北美牛和野牛中广泛出现苯并咪唑类耐药胃肠道线虫的可能性。

Assessing anthelmintic resistance risk in the post-genomic era: a proof-of-concept study assessing the potential for widespread benzimidazole-resistant gastrointestinal nematodes in North American cattle and bison.

机构信息

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

Department of Production Animal Health, University of Calgary, Faculty of Veterinary Medicine.

出版信息

Parasitology. 2020 Jul;147(8):897-906. doi: 10.1017/S0031182020000426. Epub 2020 Mar 6.

DOI:10.1017/S0031182020000426
PMID:32138794
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7391874/
Abstract

As genomic research continues to improve our understanding of the genetics of anthelmintic drug resistance, the revolution in DNA sequencing technologies will provide increasing opportunities for large-scale surveillance for the emergence of drug resistance. In most countries, parasite control in cattle and bison has mainly depended on pour-on macrocyclic lactone formulations resulting in widespread ivermectin resistance. Consequently, there is an increased interest in using benzimidazole drugs which have been used comparatively little in cattle and bison in recent years. This situation, together with our understanding of benzimidazole resistance genetics, provides a practical opportunity to use deep-amplicon sequencing to assess the risk of drug resistance emergence. In this paper, we use deep-amplicon sequencing to scan for those mutations in the isotype-1 β-tubulin gene previously associated with benzimidazole resistance in many trichostrongylid nematode species. We found that several of these mutations occur at low frequency in many cattle and bison parasite populations in North America, suggesting increased use of benzimidazole drugs in cattle has the potential to result in widespread emergence of resistance in multiple parasite species. This work illustrates a post-genomic approach to large-scale surveillance of early emergence of anthelmintic resistance in the field.

摘要

随着基因组研究继续深入了解抗蠕虫药物耐药性的遗传学,DNA 测序技术的革命将为大规模监测耐药性的出现提供越来越多的机会。在大多数国家,牛和野牛的寄生虫控制主要依赖于浇泼式大环内酯类制剂,导致伊维菌素广泛耐药。因此,人们越来越感兴趣地使用苯并咪唑类药物,近年来在牛和野牛中使用相对较少。这种情况,再加上我们对苯并咪唑类药物耐药性遗传学的了解,为使用深度扩增子测序来评估耐药性出现的风险提供了一个实际的机会。在本文中,我们使用深度扩增子测序来扫描先前与许多三刺线虫种的苯并咪唑耐药性相关的同工型 1β-微管蛋白基因中的那些突变。我们发现,这些突变中的几个在北美的许多牛和野牛寄生虫种群中以低频率发生,这表明在牛中增加苯并咪唑类药物的使用有可能导致多种寄生虫物种的耐药性广泛出现。这项工作说明了一种后基因组方法,可以大规模监测田间抗蠕虫药物耐药性的早期出现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd05/10317676/47d12b65e07b/S0031182020000426_fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd05/10317676/69aa32e18a87/S0031182020000426_fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd05/10317676/9a3b327ac087/S0031182020000426_fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd05/10317676/47d12b65e07b/S0031182020000426_fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd05/10317676/69aa32e18a87/S0031182020000426_fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd05/10317676/9a3b327ac087/S0031182020000426_fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd05/10317676/47d12b65e07b/S0031182020000426_fig3.jpg

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