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Molecular and phenotypic characterisation of fenbendazole resistance in a field-derived isolate of Ostertagia ostertagi
Veterinary Parasitology ( IF 2.0 ) Pub Date : 2020-11-13 , DOI: 10.1016/j.vetpar.2020.109319
Dave J. Bartley , Natalie J. Jewell , Leigh M. Andrews , Sian Mitchell , Alison A. Morrison

The prevalence of anthelmintic resistance in the bovine nematode Cooperia oncophora has been well documented globally but lack of efficacy against the more pathogenic nematode species Ostertagia ostertagi is less common. The sensitivity of an O. ostertagi isolate to the benzimidazole class of anthelmintic was investigated using classical parasitological techniques following apparent clinical failure of controlled release fenbendazole capsule administration in first season grazers at pasture. A controlled efficacy test (CET) was conducted in conjunction with sequencing of the β-tubulin isotype 1 gene of larvae pre- and post-fenbendazole administration. Twelve helminth-naïve calves were infected experimentally with 20,000 third stage larvae; six received oral fenbendazole (7.5 mg/kg bodyweight) 28 days post infection. Total abomasal nematode burdens were compared between treatment and control groups to determine efficacy. Fenbendazole resistance in O. ostertagi was confirmed with a total treatment failure in reducing worm burden: efficacy of 0%. Sequence analysis of the β-tubulin isotype-1 gene from forty-five infective larvae from both control and treated groups was performed. The three commonest single nucleotide polymorphisms (SNPs) associated with benzimidazole resistance, namely F167Y, E198A and F200Y, were examined. The predominant resistance-associated SNPs were F200Y (78 % control and 79 % treated groups) and F167Y (remaining genotypes) and emphasises the importance of these SNPs in clinical disease in this isolate. The development of diagnostic molecular tools based on a characterised field-derived isolate of benzimidazole-resistant Ostertagia will enable future prevalence surveys to be undertaken to assess the possible risk posed by resistance in this economically important species.



中文翻译:

在田间分离的Ostertagia ostertagi菌株中对芬苯达唑耐药的分子和表型特征

牛线虫Cooperia oncophora的驱虫抗药性在全球已有广泛报道,但对更具致病性的线虫种类Ostertagia ostertagi缺乏药效较不普遍。O.ostertagi的敏感性在牧场的第一季放牧者中,使用控释芬苯达唑胶囊明显出现临床失败后,使用经典的寄生虫学技术研究了分离到苯并咪唑类驱虫药的方法。结合芬苯达唑给药前后幼虫的β-微管蛋白同种型1基因的测序进行了对照功效测试(CET)。十二只幼稚的幼虫被实验性地感染了20,000只第三期幼虫。感染后28天,六名接受口服芬苯达唑(7.5毫克/千克体重)。在治疗组和对照组之间比较总的线虫线虫负担,以确定疗效。费氏曲霉对芬苯达唑的抗药性证实在减少蠕虫负担方面总的治疗失败:功效为0%。对来自对照组和治疗组的四十五个感染性幼虫的β-tubulinisotype-1基因进行序列分析。研究了与苯并咪唑抗性相关的三个最常见的单核苷酸多态性(SNP),即F167Y,E198A和F200Y。与抗药性相关的主要SNP为F200Y(对照组为78%,治疗组为79%)和F167Y(其余基因型),并强调了这些SNP在此分离株中在临床疾病中的重要性。基于对苯并咪唑耐药的雄激素性病原性分离株的诊断性分子工具的开发 将使未来的流行率调查得以进行,以评估这种重要经济物种中抗药性可能带来的风险。

更新日期:2020-11-27
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