Von Samson-Himmelstjerna G, Blackhall W J, McCarthy J S, Skuce P J
Institute for Parasitology, University of Veterinary Medicine Foundation, Bünteweg 17, Hannover 30559, Germany.
Parasitology. 2007;134(Pt 8):1077-86. doi: 10.1017/S0031182007000054.
Resistance to the benzimidazole class of anthelmintics in nematodes of veterinary importance has a long history. Research into the mechanisms responsible for this resistance is subsequently at a more advanced stage than for other classes of anthelmintics. The principal mechanism of resistance to benzimidazoles is likely to involve changes in the primary structure of beta-tubulins, the building blocks of microtubules. Specifically, point mutations in the beta-tubulin isotype 1 gene leading to amino acid substitutions in codons 167, 198, and 200 of the protein have been associated with resistance in nematodes. These single nucleotide polymorphisms offer a means of detecting the presence of resistance within populations. In this mini-review, we focus on the prevalence and importance of these polymorphisms in three groups of nematodes: trichostrongylids, cyathostomins, and hookworms. A brief overview of existing strategies for genotyping single nucleotide polymorphisms is also presented. The CARS initiative hopes to exploit these known polymorphisms to further our understanding of the phenomenon of BZ resistance.
兽医领域重要线虫对苯并咪唑类驱虫药产生抗药性已有很长历史。随后,针对这种抗药性产生机制的研究比针对其他类驱虫药的研究处于更先进的阶段。对苯并咪唑类药物产生抗药性的主要机制可能涉及β-微管蛋白(微管的组成成分)一级结构的变化。具体而言,β-微管蛋白同型体1基因中的点突变导致该蛋白第167、198和200位密码子的氨基酸替换,这与线虫的抗药性有关。这些单核苷酸多态性提供了一种检测种群中抗药性存在情况的方法。在本综述中,我们重点关注这些多态性在三类线虫中的流行情况和重要性:毛圆线虫、盅口线虫和钩虫。还简要概述了现有的单核苷酸多态性基因分型策略。CARS计划希望利用这些已知的多态性来进一步加深我们对BZ抗药性现象的理解。