Zhang Yanmin, Wen Haifeng, Zhang Hao, Liu Hao, Zhang Lili, Lu Jing, Luo Chagan, Chen Mulan, Wu Weijie, Wang Wenlong, Wang Yu, Liu Chunxia
College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot, Inner Mongolia, China.
Hinggan league Agricultural and Animal Husbandry Technology Extension Centre, Hinggan, Inner Mongolia, China.
Sci Rep. 2025 Aug 11;15(1):29344. doi: 10.1038/s41598-025-14909-w.
Haemonchus contortus is widely distributed in the world, which is seriously harmful to small ruminants and has serious resistance to common anthelmintics. Over time, the prevalence and intensity of host infection with this parasite have gradually increased, so it is necessary to study the phylogenetic and genetic changes of single anthelmintic resistant strains. This study is the first to analyze the genetic diversity and population structure about IVM-resistant H.contortus (L3,egg, adult, n = 30 ) in Inner Mongolia, China. The H.contortus were identified to IVM resistance and cultured by fecal egg count reduction test, larval development inhibition test and larval locomotor behaviour test. The complete sequence of ITS2 ( second internal transcribed spacer ) and partial sequence of nad4 ( nicotinamide dehydrogenase subunit 4 gene ) in L3, adult and egg were amplified. At the same time, compared with the ITS2 and nad4 partial sequences of H.contortus reported in NCBI database to carry out phylogenetic analysis and haplotype determination, so as to further study the variation and population genetic diversity of IVM-RR samples. The samples were identified as H.contortus resistant to IVM. Phylogenetic analyses of ITS2 of IVM-RR and other H.contortus showed that they were from the same branch, genetic relationship was close, the intraspecific was relatively conserved, and no significant correlation with AR. There was no significant difference between different stages of development of the samples. In addition, from the 30 nad4 gene sequences of IVM-RR samples obtained 13 haplotypes, and the 169th base site in 70% of the nad4 gene was mutated. The nucleotide diversity was 0.00623 and haplotype diversity was 0.926. IVM-RR compared with five countries' H.contortus nad4, found that the genetic differentiation level of the IVM-RR population was relatively low with the China and Pakistan populations, and the Fixation index (Fst) were 0.10957 and 0.17262, respectively. The genetic differentiation levels with Bangladesh, Greece and France populations were higher, and the Fst values were 0.46978,0.61825 and 0.98101. Perhaps the population structure differentiation were correlated with regional localization and anthelmintic frequency treatment. In this report, we analyzed the genetic diversity and population differentiation of IVM resistant H.contortus at different developmental stages, and obtained resistant samples' haplotypes, hoping to provide a new direction for the study of AR and vaccine research.
捻转血矛线虫在世界范围内广泛分布,对小型反刍动物危害严重,且对常见驱虫药具有严重抗性。随着时间的推移,宿主感染这种寄生虫的流行率和感染强度逐渐增加,因此有必要研究单一抗驱虫药菌株的系统发育和遗传变化。本研究首次分析了中国内蒙古地区对伊维菌素耐药的捻转血矛线虫(L3、虫卵、成虫,n = 30)的遗传多样性和种群结构。通过粪便虫卵计数减少试验、幼虫发育抑制试验和幼虫运动行为试验,鉴定捻转血矛线虫对伊维菌素耐药并进行培养。扩增了L3、成虫和虫卵中ITS2(第二内部转录间隔区)的完整序列和nad4(烟酰胺脱氢酶亚基4基因)的部分序列。同时,与NCBI数据库中报道的捻转血矛线虫的ITS2和nad4部分序列进行比较,进行系统发育分析和单倍型测定,以进一步研究伊维菌素抗性样本的变异和种群遗传多样性。样本被鉴定为对伊维菌素耐药的捻转血矛线虫。对伊维菌素抗性和其他捻转血矛线虫的ITS2进行系统发育分析表明,它们来自同一分支,亲缘关系密切,种内相对保守,与抗药性无显著相关性。样本不同发育阶段之间无显著差异。此外,从30条伊维菌素抗性样本的nad4基因序列中获得了13个单倍型,70%的nad4基因中的第169个碱基位点发生了突变。核苷酸多样性为0.00623,单倍型多样性为0.926。将伊维菌素抗性样本与五个国家的捻转血矛线虫nad4进行比较,发现伊维菌素抗性种群与中国和巴基斯坦种群的遗传分化水平相对较低,固定指数(Fst)分别为0.10957和0.17262。与孟加拉国、希腊和法国种群的遗传分化水平较高,Fst值分别为0.46978、0.61825和0.98101。也许种群结构分化与区域定位和驱虫药治疗频率有关。在本报告中,我们分析了不同发育阶段对伊维菌素耐药的捻转血矛线虫的遗传多样性和种群分化,并获得了抗性样本的单倍型,希望为抗药性研究和疫苗研究提供新的方向。