Nematode ligand-gated chloride channels: an appraisal of their involvement in macrocyclic lactone resistance and prospects for developing molecular markers
Nematode ligand-gated chloride channels: an appraisal of their involvement in macrocyclic lactone resistance and prospects for developing molecular markers
复制标题
DOI：
10.1017/s0031182007000042
复制
发表时间：
2007-01-01
期刊：
影响因子：
2.4
通讯作者：
Wolstenholme, A. J.
中科院分区：
文献类型：
--
作者：
McCavera, S.;Walsh, T. K.;Wolstenholme, A. J.
配体门控氯通道，包括谷氨酸-（葡萄糖）和gaba门控通道，是大环内酯（ML）家族驱虫药的靶点。在秀丽隐杆线虫和黑腹果蝇等实验室模型中，这些通道序列和表达的变化可引起对ML的耐药性。秀丽隐杆线虫的高水平ML抗性需要多个葡萄糖亚基基因的突变，这可能受到间隙连接和两栖类基因的额外突变的影响。寄生线虫具有与秀丽隐杆线虫不同的通道亚基基因补体，但包括avr-14在内的一些基因广泛存在。在嗜血库伯（Cooperia oncophora）中发现了avr-14同源物的多态性，这使得该亚基对伊维菌素和谷氨酸不那么敏感，并且在耐药的扭曲血蜱（Haemonchus扭曲血蜱）分离株中也报道了几个亚基的多态性。这导致了ML抗性可能是多基因的建议。本文探讨了可能的原因及其对耐药性分子测试发展的影响。
Ligand-gated chloride channels, including the glutamate-(GluCl) and GABA-gated channels, are the targets of the macrocyclic lactone (ML) family of anthelmintics. Changes in the sequence and expression of these channels can cause resistance to the ML in laboratory models, such as Caenorhabditis elegans and Drosophila melanogaster. Mutations in multiple GluCl subunit genes are required for high-level ML resistance in C. elegans, and this can be influenced by additional mutations in gap junction and amphid genes. Parasitic nematodes have a different complement of channel subunit genes from C. elegans, but a few genes, including avr-14, are widely present. A polymorphism in an avr-14 orthologue, which makes the subunit less sensitive to ivermectin and glutamate, has been identified in Cooperia oncophora, and polymorphisms in several subunits have been reported from resistant isolates of Haemonchus contortus. This has led to suggestions that ML resistance may be polygenic. Possible reasons for this, and its consequences for the development of molecular tests for resistance, are explored.