PDF(Pubmed)
Abstract：
Parasitic gastrointestinal nematodes pose significant health risks to humans, livestock, and companion animals, and their control relies heavily on the use of anthelmintic drugs. Overuse of these drugs has led to the emergence of resistant nematode populations. Herein, a naturally occurring isolate (referred to as BCR) of the dog hookworm, Ancylostoma caninum, that is resistant to 3 major classes of anthelmintics is characterized. Various drug assays were used to determine the resistance of BCR to thiabendazole, ivermectin, moxidectin and pyrantel pamoate. When compared to a drug-susceptible isolate of A. caninum, BCR was shown to be significantly resistant to all 4 of the drugs tested. Multiple single nucleotide polymorphisms have been shown to impart benzimidazole resistance, including the F167Y mutation in the β-tubulin isotype 1 gene, which was confirmed to be present in BCR through molecular analysis. The frequency of the resistant allele in BCR was 76.3% following its first passage in the lab, which represented an increase from approximately 50% in the founding hookworm population. A second, recently described mutation in codon 134 (Q134H) was also detected at lower frequency in the BCR population. Additionally, BCR exhibits an altered larval activation phenotype compared to the susceptible isolate, suggesting differences in the signalling pathways involved in the activation process which may be associated with resistance. Further characterization of this isolate will provide insights into the mechanisms of resistance to macrocyclic lactones and tetrahydropyrimidine anthelmintics.
摘要：
寄生胃肠线虫对人类构成重大健康风险,牲畜,和伴侣动物，他们的控制在很大程度上依赖于驱虫药的使用。这些药物的过度使用导致了抗性线虫种群的出现。在这里，狗钩虫的天然分离物（称为BCR），犬囊造孔,这是耐3类主要驱虫药的特点。使用各种药物测定来确定BCR对噻菌灵的抗性，伊维菌素,莫西丁和pamoate吡喃酮。当与一种对药物敏感的犬曲霉分离株相比时，显示BCR对所有4种测试的药物具有显著抗性。多个单核苷酸多态性已被证明赋予苯并咪唑抗性，包括β-微管蛋白同种型1基因中的F167Y突变，通过分子分析证实其存在于BCR中。在实验室中首次传代后，BCR中抗性等位基因的频率为76.3％，从创始钩虫种群的大约50％增加。一秒,最近描述的密码子134(Q134H)突变也在BCR人群中以较低的频率检测到.此外,与易感分离株相比，BCR显示出幼虫激活表型的改变，这表明参与激活过程的信号通路存在差异，这可能与抗性有关。该分离物的进一步表征将提供对大环内酯和四氢嘧啶驱虫药的抗性机制的见解。
