Sea lice resistance to avermectins

该计划的长期目标是制定策略，以识别、监测和控制海虱对鲑鱼养殖中使用的治疗突变体的抗药性，重点是增加我们对海虱生物学的知识，特别是与海虱-鲑鱼相互作用有关的知识，以便更有效地控制海虱。短期目标是增加我们对阿维菌素、阿维菌素苯甲酸酯(EMB；Slice)的作用机制的了解，目前用于控制海虱的主要药物。这项研究将加深我们对阿维菌素在海虱中的作用以及抗药性如何发展的理解。这是一个基础研究项目，其应用与鲑鱼水产养殖业直接相关。具体目标是进一步了解药物是如何从鲑鱼皮肤进入海虱的目标部位，以及这种运输是如何控制的。我们还想知道阿维菌素是如何杀死海虱的，并想知道更多关于目标部位的信息。这两个参数也都对抗药性的发展有影响。摄取减少会导致靶部位可用药物减少，从而降低疗效。受体结构的变化也会导致疗效降低。了解阿维菌素的作用机制可能为开发控制海虱的新药提供基础，特别是如果阿维菌素的靶点不同于其他节肢动物。如果对海虱抗药性机制的了解增加，将能够更快地检测抗药性的发展以及改进的治疗策略。

The Long Term Goal of this program is to develop strategies to identify, monitor, and control resistance of sea lice to therapeutants used in salmonid aquaculture with a focus on increasing our knowledge of sea lice biology, especially as it relates to sea lice-salmon interactions so that sea lice can be controlled more effectively.  The Short-Term Objective is to increase our understanding of the mechanisms of action of the avermectin, emamectin benzoate (EMB; SLICE), currently the predominant drug used for sea lice control. This study will enhance our understanding of how avermectins act in sea lice and how drug resistance can develop.  This is a basic research program with applications directly relevant to the salmonid aquaculture industry. Specific goals are to further understand how the drug gets from the salmon skin to the target site in sea lice and how this transport is controlled.  We also want to know exactly how the avermectins kill sea lice and want to know more about the target site.  Both these parameters also have implications in resistance development. Decreased uptake would lead to less drug available at the target site and thus decreased efficacy.  Changes in receptor structure would also result in decreased efficacy. Understanding the mechanisms of avermectin action may provide the basis for novel drug development for sea lice control, especially if the target for avermectins is different than for other arthropods.  Increased understanding of sea lice resistance mechanisms would allow for more rapid detection of resistance development as well as improved therapeutic strategies.