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首页> 外文期刊>International Journal for Parasitology: Drugs and Drug Resistance >Evaluation of changes in drug susceptibility and population genetic structure in Haemonchus contortus following worm replacement as a means to reverse the impact of multiple-anthelmintic resistance on a sheep farm
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Evaluation of changes in drug susceptibility and population genetic structure in Haemonchus contortus following worm replacement as a means to reverse the impact of multiple-anthelmintic resistance on a sheep farm

机译:评估蠕虫替代后蠕动造成的药物敏感性和群体遗传结构的变化作为逆转绵羊农场的多重抑制抗性影响的手段

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A population of Haemonchus contortus that was highly resistant to benzimidazoles and avermectin/milbemycins with a subpopulation that was resistant to levamisole, was replaced with a susceptible laboratory isolate of H. contortus in a flock of sheep . The anthelmintic susceptibility and population genetics of the newly established population were evaluated for 3.5 years using in vivo , in vitro , and molecular methods. Successful replacement of the resistant population with a susceptible population was confirmed using phenotypic and genotypic measurements; larval development assay indicated full anthelmintic susceptibility; albendazole treatment yielded 98.7% fecal egg count reduction; pyrosequence genotyping of single nucleotide polymorphisms in positions 167 and 200 of the isotype-1 beta tubulin gene were present at 0.0 and 1.7%, respectively; microsatellite genotyping indicated the background haplotype was similar to the susceptible isolate; and haplotypes of the isotype-1 beta tubulin gene were similar to the susceptible isolate. To sustain the susceptibility of the new population, targeted selective treatment was implemented using albendazole. Surprisingly, within 1.5 years post-replacement, the population reverted to a resistant phenotype. Resistance to albendazole, ivermectin, and moxidectin was confirmed via fecal egg count reduction test, larval development assay, and pyrosequencing-based genotyping. Targeted selective treatment was then carried out using levamisole. However, within one year, resistance was detected to levamisole. Population genetics demonstrated a gradual change in the genetic structure of the population until the final population was similar to the initial resistant population. Genetic analyses showed a lack of diversity in the susceptible isolate, suggesting the susceptible isolate had reduced environmental fitness compared to the resistant population, providing a possible explanation for the rapid reversion to resistance. This work demonstrates the power of combining molecular, in vitro , and in vivo assays to study phenotypic and genotypic changes in a field population of nematodes, enabling improved insights into the epidemiology of anthelmintic resistance.
机译:一种患有对苯并咪唑和Avermectin / Milbemycins具有高度抗性的Haemonchus intortus,用贫苯甲醚抑制的贫民素被置换在一群绵羊中的敏感实验室分离物。在体内,体外和分子方法中评估新已建立的人群的血清敏感性和群体遗传学。使用表型和基因型测量确认,确认使用易感群体的抗性群体的成功替代;幼虫发展测定表明全部的敏感性易感性;阿贝唑治疗产生98.7%的粪便鸡蛋计数减少;单一核苷酸在同种型-1β管蛋白基因的位置167和200中的单核苷酸多态性的脱毛基因分型分别为0.0和1.7%;微卫星基因分型表明,背景单倍型类似于易感隔离物;并且同种型-1β小管蛋白基因的单倍型类似于敏感的分离物。为了维持新人群的易感性,使用阿比萨唑实施有针对性的选择性治疗。令人惊讶的是,在替代后1.5年内,人口恢复到抗性表型。通过粪卵计数降低试验,幼虫发育测定和基于焦肌型基因分型证实了对阿伦唑,伊维霉菌素和莫昔唑啉的抵抗力。然后使用左旋吲哚进行靶向选择性处理。然而,在一年内,检测到左偏石。人口遗传学证明了人口遗传结构的逐步变化,直到最终群体与初始抗性群体相似。遗传分析显示易感孤立中缺乏多样性,表明与抗性群体相比,易感分离物减少了环境健康,提供了对抗性的快速逆转的可能解释。这项工作展示了组合分子,体外和体内测定的力量,以研究线虫野外群体的表型和基因型变化,从而能够改善抗性抗性的流行病学的见解。

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