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

鲑鱼虱是一种重要的体外寄生虫，具有重要的生态和经济意义。海虱每年给海水鲑鱼养殖业造成数百万美元的损失，还会对野生鲑鱼种群造成负面影响。在过去的二十年里，关于海虱的最大新出现的问题可能是对化学处理产生抗药性。所有主要三文鱼生产国(即挪威、苏格兰、智利、加拿大等)已经观察到抗寄生虫治疗的有效性下降，以及虱子抗药性品系的发展。在加拿大东部，主要的影响是阿维菌素苯甲酸酯的药效降低(Jones等人，2012年)，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)发现了与该药物药效降低有关的虱子基因簇。目前，加拿大缺乏不同种类和不同作用模式的化合物来治疗海虱，然而，在其他国家也出现了使用有机磷和拟除虫菊酯的情况，并且也出现了耐药性发展的问题。为了解决全球在有效管理海虱工具方面的这一差距，Elanco Animal Health开发了一种饲料疗法(Lufenuron)，用于在孵化场管理海虱，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，以确定该开发产品赋予的保护期。目前工作的目标是确定氟苯脲在海虱中的作用模式(MOA)和潜在的未来耐药机制。这将通过(1)确定氟苯脲对沙门氏菌生活史的生理影响，(2)确定与沙门氏菌种群对氟苯脲抗性相关的基因/基因类型，以及(3)开发针对氟苯脲的模型框架来确定不同养殖区的遗传交互作用，从而实现这一目标。

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.