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.
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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DOI：
10.1016/j.ijpddr.2021.02.004
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发表时间：
2021-04
期刊：
影响因子：
--
通讯作者：
Kaplan RM
中科院分区：
文献类型：
--
作者：
George MM;Vatta AF;Howell SB;Storey BE;McCoy CJ;Wolstenholme AJ;Redman EM;Gilleard JS;Kaplan RM
对苯并咪唑类和阿维菌素/米尔倍霉素高度耐药的捻转血矛线虫种群，以及对左旋咪唑耐药的亚群，用敏感的H.在羊群中扭动。使用体内、体外和分子方法对新建立的种群的驱虫药敏感性和种群遗传学进行了为期3.5年的评价。利用表型和基因型测量证实了用敏感种群成功地替换了抗性种群;幼虫发育试验表明完全对驱虫剂敏感;阿苯达唑治疗产生了98.7%的粪便虫卵计数减少;同种型1 β微管蛋白基因的位置167和200的单核苷酸多态性的焦磷酸序列基因分型分别为0.0%和1.7%;微卫星基因分型结果显示，背景单倍型与敏感株相似，同种型1 β微管蛋白基因单倍型与敏感株相似。为了维持新人群的敏感性，使用阿苯达唑进行靶向选择性治疗。令人惊讶的是，在置换后1.5年内，该群体恢复为耐药表型。通过粪便虫卵计数减少试验、幼虫发育试验和基于焦磷酸测序的基因分型证实了对阿苯达唑、伊维菌素和莫昔克丁的耐药性。然后使用左旋咪唑进行靶向选择性治疗。然而，在一年内，检测到对左旋咪唑的耐药性。群体遗传学表明，在群体的遗传结构的逐渐变化，直到最终的人口是相似的初始抗性群体。遗传分析表明，在敏感的分离物缺乏多样性，这表明敏感的分离物减少了环境适应性相比，耐药人口，提供了一个可能的解释，快速恢复到电阻。这项工作证明了结合分子，体外和体内测定研究线虫的田间种群的表型和基因型变化的能力，从而提高了对驱虫药耐药性流行病学的认识。
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.
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影响因子：
1.1
作者：
MARTIN, PJ;ANDERSON, N;JARRETT, RG
通讯作者：
JARRETT, RG
DOI：
10.1016/j.vprsr.2017.04.007
发表时间：
2017-08-01
期刊：
Veterinary parasitology, regional studies and reports
影响因子：
--
作者：
Herrera-Manzanilla, F A;Ojeda-Robertos, N F;Torres-Acosta, J F J
通讯作者：
Torres-Acosta, J F J
影响因子：
10.7
作者：
Bryant, D;Moulton, V
通讯作者：
Moulton, V
影响因子：
4
作者：
Kaplan, R. M.;Vidyashankar, A. N.;Terrill, T. H.
通讯作者：
Terrill, T. H.
影响因子：
1.3
作者：
Noel, Marie L.;Scare, Jessica A.;Nielsen, Martin K.
通讯作者：
Nielsen, Martin K.