Responses of sea lice to novel parasiticides and their differing modes of action

鲑鱼虱（Lepeophtheirus salmonis，桡足目：鲑鱼科）是一种重要的生态和经济寄生虫。海虱每年给海洋鲑鱼养殖业造成数百万美元的损失，也会对野生鲑鱼种群产生负面影响。在过去的二十年里，关于海虱最大的新问题可能是对化学处理的抗药性的发展。所有主要鲑鱼生产国（即挪威、苏格兰、智利、加拿大等）都观察到抗寄生虫治疗的效果下降，并且出现了抗性虱子菌株。在加拿大东部，观察到的主要影响是苯甲酸埃马菌素的疗效降低（Jones等人，2012），最近我们的研究小组在加拿大太平洋地区（不列颠哥伦比亚省）发现了与该药物疗效降低相关的虱子基因簇。目前，加拿大缺乏用于治疗海虱的不同类别和不同作用方式的化合物，然而，其他国家也在使用有机磷酸酯和拟除虫菊酯，并且也显示出耐药性发展的问题。为了弥补全球在海虱有效管理工具方面的这一差距，Elanco动物保健公司开发了一种针对海虱的饲料内治疗（lufenuron），将在孵化场使用，并为鲑鱼提供长期保护，使其免受海上感染。Lufenuron目前正在加拿大、智利和挪威进行临床试验，以确定开发产品赋予的保护期。目前工作的目标是确定氟虫腈对海虱的作用模式（MoA）和潜在的未来耐药机制。这将通过(1)确定氟虫腈对沙门氏菌生命周期的生理影响，(2)确定与氟虫腈抗性相关的基因/基因型，以及(3)开发氟虫腈特异性建模框架以确定不同养殖区域的遗传相互作用来实现。

Salmon lice, Lepeophtheirus salmonis (Copepoda: Caligidae), are important ectoparasites both ecologically and economically. Sea lice cause multi-million dollar losses to the marine salmon aquaculture industry each year, and can negatively impact wild stocks of salmonids as well. Over the past two decades perhaps the greatest emerging issue with respect to sea lice has been the development of resistance to chemical treatment. All of the major salmon producing countries (i.e. Norway, Scotland, Chile, Canada, etc.) have observed declines in efficacy of anti-parasitic treatments, and development of resistant strains of lice. Within Eastern Canada, the major impact has been observed in reduced efficacy of emamectin benzoate (Jones et al, 2012), and recently our research group has identified louse gene clusters associated with reduced efficacy of this drug in Pacific Canada (British Columbia). Currently there is a lack of compounds of different classes and different modes of action for treatment of sea lice in Canada, however, use of organophosphates and pyrethroids occurs in other countries, and have also exhibited issues with resistance development. In order to target this gap in effective management tools for sea lice globally, Elanco Animal Health has developed an in-feed treatment (lufenuron) against sea lice to be administered at the hatchery and provide long-term protection of salmon against infection at sea. Lufenuron is currently undergoing clinical trials in Canada, Chile and Norway, to determine the protection period conferred by the developmental product. It is the goal of the current work to identify the mode of action (MoA) of lufenuron in sea lice and potential future mechanisms of drug resistance. This will be achieved through (1) Determining physiological impacts of lufenuron on the life cycle of L. salmonis, (2) Identifying genes/genotypes associated with resistance to lufenuron in L. salmonis populations, and (3) Developing a lufenuron-specific modelling framework to identify genetic interactions in different farming regions.