Recent reports of monepantel (MPTL) resistance in UK field isolates of Teladorsagia circumcincta has highlighted the need for a better understanding of the mechanism of MPTL-resistance in order to preserve its anthelmintic efficacy in this economically important species. Nine discrete populations of T. circumcincta were genotypically characterised; three MPTL-susceptible isolates, three experimentally selected MPTL-resistant strains and three field derived populations. Full-length Tci-mptl-1 gene sequences were generated and comparisons between the MPTL-susceptible isolates, MPTL-resistant strains and one field isolate, showed that different putative MPTL-resistance conferring mutations were present in different resistant isolates. Truncated forms of the Tci-mptl-1 gene were also observed. The genetic variability of individual larvae, within and between populations, was examined using microsatellite analyses at 10 'neutral' loci (presumed to be unaffected by MPTL). Results confirmed that there was little background genetic variation between the populations, global FST <0.038. Polymorphisms present in exons 7 and 8 of Tci-mptl-1 enabled genotyping of individual larvae. A reduction in the number of genotypes was observed in all MPTL-resistant strains compared to the MPTL-susceptible strains that they were derived from, suggesting there was purifying selection at Tci-mptl-1 as a result of MPTL-treatment. The potential link between benzimidazole (BZ)-resistance and MPTL-resistance was examined by screening individual larvae for the presence of three SNPs associated with BZ-resistance in the β-tubulin isotype-1 gene. The majority of larvae were BZ-susceptible homozygotes at positions 167 and 198. Increased heterozygosity at position 200 was observed in the MPTL-resistant strains compared to their respective MPTL-susceptible population. There was no decrease in the occurrence of BZ-resistant genotypes in larvae from each population. These differences, in light of the purifying selection at this locus in all MPTL-resistant isolates, suggests that Tci-mptl-1 confers MPTL-resistance in T. circumcincta, as in Haemonchus contortus, but that different mutations in Tci-mptl-1 can confer resistance in different populations.

中文翻译：

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Teladorsagiacircincta 历史菌株和新衍生田间菌株中莫奈太尔抗性的基因型特征。

最近有关英国田间分离株 Teladorsagiacircincta 中莫奈太尔 (MPTL) 耐药性的报告强调，需要更好地了解 MPTL 耐药机制，以保持其在这一经济重要物种中的驱虫功效。对九个离散的 T.circumcincta 种群进行了基因型表征；三个 MPTL 敏感分离株、三个实验选择的 MPTL 抗性菌株和三个野外衍生群体。生成了全长 Tci-mptl-1 基因序列，并且对 MPTL 敏感分离株、MPTL 抗性菌株和一种野外分离株之间的比较表明，不同的假定 MPTL 抗性赋予突变存在于不同的抗性分离株中。还观察到 Tci-mptl-1 基因的截短形式。使用微卫星分析对 10 个“中性”基因座（假定不受 MPTL 影响）检查种群内和种群间个体幼虫的遗传变异性。结果证实，人群之间几乎没有背景遗传变异，总体 FST <0.038。Tci-mptl-1 外显子 7 和 8 中存在的多态性使得能够对个体幼虫进行基因分型。与它们来源的 MPTL 敏感菌株相比，在所有 MPTL 抗性菌株中观察到基因型数量减少，表明由于 MPTL 处理，Tci-mptl-1 存在纯化选择。通过筛选个体幼虫的 β-微管蛋白同种型 1 基因中是否存在与 BZ 抗性相关的三个 SNP，检查了苯并咪唑 (BZ) 抗性和 MPTL 抗性之间的潜在联系。大多数幼虫在位置 167 和 198 处是 BZ 敏感纯合子。与各自的 MPTL 敏感群体相比，在 MPTL 抗性菌株中观察到位置 200 处的杂合性增加。每个种群的幼虫中 BZ 抗性基因型的发生率没有减少。根据所有 MPTL 抗性分离株中该位点的纯化选择，这些差异表明 Tci-mptl-1 在环环线虫中赋予 MPTL 抗性，如捻转血矛线虫，但 Tci-mptl-1 中的不同突变可以赋予不同人群抵抗力。