Sea lice resistance to avermectins

该项目的长期目标是制定策略，以识别、监测和控制海虱对鲑科水产养殖中使用的治疗剂的耐药性，重点是增加我们对海虱生物学的认识，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的作用机制的理解，阿维菌素苯甲酸酯（EMB； SLICE），目前主要用于海虱控制药物。这项研究将增强我们对阿维菌素如何在海虱中起作用以及如何产生耐药性的理解。这是一个基础研究项目，其应用与鲑科水产养殖业直接相关。具体目标是进一步了解药物如何从鲑鱼皮到达海虱的目标部位，以及如何控制这种运输。我们还想确切地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。这两个参数对耐药性的发展也有影响。摄取减少会导致靶向部位可用药物减少，从而降低疗效。受体结构的改变也会导致药效下降。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作用靶点与其他节肢动物不同。加深对海虱耐药机制的了解将有助于更快地发现耐药的发展，并改进治疗策略。

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.