Avermectin/milbemycin resistance in trichostrongyloid nematodes
Avermectin/milbemycin resistance in trichostrongyloid nematodes
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DOI：
10.1016/s0020-7519(98)00068-x
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发表时间：
1998-06-01
影响因子：
4
通讯作者：
Lacey, E
中科院分区：
文献类型：
--
作者：
Gill, JH;Lacey, E
绵羊常见的毛线虫寄生虫对左旋咪唑和苯并咪唑的耐药性似乎是通过一种或最多两种机制实现的。对于阿维菌素/米霉素驱虫药类，情况更为复杂。采用游离期毛线虫体外实验研究阿维菌素/米贝霉素的构效关系。弓形Haemonchus， Trichostrongylus colbriformis和Ostertagia circulincta对阿维菌素/米尔贝霉素敏感的分离株对阿维菌素/米尔贝霉素抑制幼虫发育和L3运动的内在敏感性存在差异，但对这三种物种的结构-活性谱相似。体内阿维菌素/米尔贝霉素耐药与阿维菌素/米尔贝霉素敏感性降低有关，在一些（但不是全部）分离株中，阿维菌素/米尔贝霉素抑制了幼虫的运动和/或发育。当观察到对阿维菌素/米尔贝霉素抑制幼虫发育的敏感性降低时，不同组的耐药菌株表现出不同的结构-活性谱。许多阿维菌素/米贝霉素耐药分离株显示对对苯二甲酰胺的敏感性增加。这些体外数据使得对阿维菌素/米贝霉素耐药的分离株可以分为许多不同的类型。对两种耐药类型阿维菌素/米尔贝霉素耐药遗传的研究表明，耐药菌株的体外差异反映了耐药机制的重要差异。用伊维菌素处理绵羊后，绵羊体内弯曲螺旋形绦虫、毛状绦虫和环切螺旋形绦虫的排出动力学表明，在体内，阿维菌素/米贝霉素对环切螺旋形绦虫的临界作用可能与导致弯曲螺旋形绦虫和环切螺旋形绦虫被消除的临界作用不同。这一观察结果为耐药菌株之间的差异提供了一些解释。如果对于不同的物种，导致驱逐的关键事件是不同的，那么由此可见，观察到的抗性机制也可能不同。(C) 1998澳大利亚寄生虫学学会。Elsevier Science Ltd.出版。
Resistance to levamisole and the benzimidazoles appears to be achieved by one or, at most, two mechanisms in the common trichostrongyloid parasites of sheep. For the avermectin/milbemycin anthelmintic class the picture is more complex. In-vitro assays employing the free-living stages of trichostrongyloid nematodes were used to investigate structure-activity relationships for the avermectins/milbemycins. While avermectin/milbemycin-susceptible isolates of Haemonchus contortus, Trichostrongylus colubriformis and Ostertagia circumcincta were found to differ in their intrinsic sensitivities to avermectin/milbemycin inhibition of larval development and L3 motility, structure-activity profiles against all three species were similar. In-vivo avermectin/milbemycin resistance was associated with a reduced sensitivity to avermectin/milbemycin inhibition of larval motility and/or development in some, but not all, isolates. Where a reduced sensitivity to avermectin/milbemycin inhibition of larval development was observed, different groups of resistant isolates displayed different structure-activity profiles. Many avermectin/milbemycin-resistant isolates showed an increased sensitivity to paraherquamide. These in-vitro data have allowed the classification of avermectin/milbemycin-resistant isolates into a number of distinct types. Study of the inheritance of avermectin/milbemycin resistance in two resistance types suggests that the in-vitro differences between resistant isolates reflect important differences in the mechanism of resistance present. The kinetics of expulsion of H. contortus, T. colubriformis and O. circumcincta from sheep following treatment with ivermectin indicate that, in vivo, the critical action of avermectins/milbemycins against O. circumcincta may be different to that which results in H. contortus and T. colubriformis elimination. This observation provides some explanation for the differences between resistant isolates. If, for different species, the critical event(s) leading to expulsion are different, then it follows that the mechanisms of resistance observed may also differ. (C) 1998 Australian Society for Parasitology. Published by Elsevier Science Ltd.