Martin R J, Robertson A P
Department of Biomedical Sciences, Iowa State University, Ames, IA 50011, USA.
Parasitology. 2007;134(Pt 8):1093-104. doi: 10.1017/S0031182007000029.
Here we review molecular information related to resistance to the cholinergic anthelmintics in nematodes. The amount of molecular information available varies between the nematode species, with the best understood so far being C. elegans. More information is becoming available for some other parasitic species. The cholinergic anthelmintics act on nematode nicotinic acetylcholine receptors located on somatic muscle cells. Recent findings demonstrate the presence of multiple types of the nicotinic receptors in several nematodes and the numerous genes required to form these multimeric proteins. Not only are the receptors the product of several genes but they are subject to modulation by several other proteins. Mutations altering these modulatory proteins could alter sensitivity to the cholinergic anthelmitics and thus lead to resistance. We also discuss the possibility that resistance to the cholinergic anthelmintics is not necessarily the result of a single mutation but may well be polygenic in nature. Additionally, the mutations resulting in resistance may vary between different species or between resistant isolates of the same species. A list of candidate genes to examine for SNPs is presented.
在此，我们综述与线虫对胆碱能驱虫药抗性相关的分子信息。现有分子信息的数量因线虫种类而异，目前了解最多的是秀丽隐杆线虫。关于其他一些寄生性线虫种类的信息也越来越多。胆碱能驱虫药作用于位于体肌细胞上的线虫烟碱型乙酰胆碱受体。最近的研究结果表明，几种线虫中存在多种类型的烟碱型受体以及形成这些多聚体蛋白所需的众多基因。这些受体不仅是多个基因的产物，而且还受到其他几种蛋白质的调节。改变这些调节蛋白的突变可能会改变对胆碱能驱虫药的敏感性，从而导致抗性。我们还讨论了对胆碱能驱虫药的抗性不一定是单个突变的结果，而很可能本质上是多基因的可能性。此外，导致抗性的突变可能在不同物种之间或同一物种的抗性分离株之间有所不同。本文列出了用于检测单核苷酸多态性的候选基因清单。
