Identifying molecular determinants of drug susceptibility in salmon lice (Lepeophtheirus salmonis)

鉴定鲑鱼虱子（Lepeophtheirus salminis）药物敏感性的分子决定因素

• 批准号: BB/L022923/1
• 负责人: Armin Sturm
• 金额: $ 61.24万
• 依托单位: University of Stirling
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2014
• 资助国家: 英国
• 起止时间: 2014 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FL022923%2F1
• 关键词: Identifying; molecular; determinants; drug; susceptibility

The salmon louse, Lepeophtheirus salmonis, is a crustacean ectoparasite infecting wild and farmed salmonid fishes, which causes significant problems in marine Atlantic salmon aquaculture. Salmon louse infections on farms require control to maintain good fish health and welfare, and to minimise potential impacts of farm-origin parasites on wild fish populations. Currently, salmon louse control on fish farms depends heavily upon the use of drugs, supplemented by farm management measures. A number of non-chemical control strategies are currently under development, and these include the biological control of lice through cleaner fish and attempts to render salmon resistant to lice through vaccination and selective breeding programmes. However, these and other alternative control strategies are presently not sufficiently developed to allow full implementation at an industrial scale.While anti-parasitic drugs offer efficient salmon louse control, relatively few types of delousing agents are available. It is known from other pests and parasites that the repeated use of the same or similar chemicals increases the risk that parasites may develop drug resistances, driven by the mechanisms of natural selection discovered by Charles Darwin. Certain genetic features, called "resistance alleles", are usually rare in organisms as they provide no benefits to their carriers under normal conditions. Parasites possessing resistance alleles, however, are able to survive drug treatments better than those without, hence if the same drug is over-used, resistance alleles can increase their frequency in treated parasite populations as susceptible individuals are killed by treatment. This may ultimately result in drug resistance of the entire population.Very little is known about the mechanisms responsible for drug resistance in salmon lice. In the proposed project, drug-resistant strains of salmon lice generated in the laboratory will be used to investigate potential resistance mechanisms. Two strategies will be followed to find out how these lice have managed to become drug resistant. Firstly, breeding crosses will be made between resistant and drug-susceptible salmon lice, and genetic sequences that are associated with resistance will be identified using the latest DNA sequencing methodologies. Secondly, differences in gene expression between resistant and drug-susceptible salmon lice will be determined, which will provide new insights into the involvement of particular molecular pathways in development of resistance to particular drugs. Such knowledge will be extremely useful in the identification of drugs which can break the resistance mechanism.Choices among available treatment options on salmon farms are currently based on the results of "bioassays", which are small-scale laboratory treatments of salmon lice used to establish susceptibility to treatment. However, salmon louse bioassays are error-prone and regularly fail to correctly predict the success of subsequent farm treatments. The present project will develop fast tests to detect genetic susceptibility to treatment that are expected to be more specific and accurate than bioassays in identifying the best treatment choice for a given farm situation. Using the best available treatment has obvious economic and environmental benefits, and can help to prevent resistance development. New, unexploited drug classes represent a limited natural resource of high value for future food security. By helping to combat the development of drug resistance, this project will help to extend the life of current and novel delousing agents, and thus improve the sustainability of intensive salmon farming.

鲑虱（Lepeophtheirus salmonis）是一种寄生于野生和养殖鲑科鱼类的甲壳类体外寄生虫，它给大西洋鲑鱼养殖业带来了严重的问题。养殖场的鲑鱼虱感染需要控制，以保持良好的鱼类健康和福利，并尽量减少养殖场来源的寄生虫对野生鱼类种群的潜在影响。目前，养鱼场的三文鱼虱控制在很大程度上依赖于药物的使用，并辅之以养殖场管理措施。目前正在制定一些非化学品控制战略，其中包括通过清洁鱼类对虱子进行生物控制，以及试图通过疫苗接种和选择性繁殖方案使鲑鱼对虱子产生抵抗力。尽管抗寄生虫药物提供了有效的鲑鱼虱控制，但可获得的除虱剂类型相对较少。从其他害虫和寄生虫得知，重复使用相同或类似的化学品会增加寄生虫产生抗药性的风险，这是由查尔斯达尔文发现的自然选择机制驱动的。某些遗传特征，称为“抗性等位基因”，通常在生物体中很罕见，因为它们在正常条件下对其携带者没有任何好处。然而，具有抗性等位基因的寄生虫能够比没有抗性等位基因的寄生虫更好地在药物治疗中存活，因此如果过度使用相同的药物，抗性等位基因可以增加它们在治疗的寄生虫种群中的频率，因为易感个体被治疗杀死。这可能最终导致整个种群的耐药性。对鲑鱼虱耐药性的机制知之甚少。在拟议的项目中，实验室产生的鲑鱼虱耐药菌株将用于研究潜在的耐药机制。将遵循两种策略，以找出这些虱子是如何设法成为耐药性。首先，将在耐药和药物敏感的鲑鱼虱之间进行育种杂交，并将使用最新的DNA测序方法来确定与耐药性相关的基因序列。其次，耐药和药物敏感的鲑鱼虱之间的基因表达的差异将被确定，这将提供新的见解参与特定的分子途径在特定药物的耐药性的发展。这些知识将是非常有用的药物，可以打破耐药性机制，鲑鱼养殖场现有的治疗方案的选择目前是基于“生物测定”的结果，这是小规模的实验室治疗鲑鱼虱用于建立敏感性的治疗。然而，鲑鱼虱生物测定是容易出错的，并且经常无法正确预测后续农场处理的成功。本项目将开发快速测试，以检测对治疗的遗传易感性，预计在确定特定农场情况的最佳治疗选择方面，这种测试比生物测定更具体和准确。采用最佳的处理方法具有明显的经济和环境效益，并有助于防止抗性的发展。新的、未开发的毒品类别是对未来粮食安全具有高价值的有限自然资源。通过帮助对抗耐药性的发展，该项目将有助于延长现有和新型除虱剂的寿命，从而提高鲑鱼集约养殖的可持续性。

项目成果

Genetic fingerprinting of salmon louse (Lepeophtheirus salmonis) populations in the North-East Atlantic using a random forest classification approach.

鲑鱼虱（Lepeophtheirus salmonis）种群在东北大西洋的遗传指纹使用随机的森林分类方法。

• DOI: 10.1038/s41598-018-19323-z
• 发表时间: 2018-01-19
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Jacobs A;De Noia M;Praebel K;Kanstad-Hanssen Ø;Paterno M;Jackson D;McGinnity P;Sturm A;Elmer KR;Llewellyn MS
• 通讯作者: Llewellyn MS

A Survey of the ATP-Binding Cassette (ABC) Gene Superfamily in the Salmon Louse (Lepeophtheirus salmonis).

• DOI: 10.1371/journal.pone.0137394
• 发表时间: 2015
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Carmona-Antoñanzas G;Carmichael SN;Heumann J;Taggart JB;Gharbi K;Bron JE;Bekaert M;Sturm A
• 通讯作者: Sturm A

Maternal inheritance of deltamethrin resistance in the salmon louse Lepeophtheirus salmonis (Krøyer) is associated with unique mtDNA haplotypes.

• DOI: 10.1371/journal.pone.0180625
• 发表时间: 2017
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Carmona-Antoñanzas G;Bekaert M;Humble JL;Boyd S;Roy W;Bassett DI;Houston RD;Gharbi K;Bron JE;Sturm A
• 通讯作者: Sturm A

MOESM4 of Genome-wide survey of cytochrome P450 genes in the salmon louse Lepeophtheirus salmonis (Krøyer, 1837)

MOESM4 对鲑鱼虱子 Lepeophtheirus Salmonis 中的细胞色素 P450 基因进行全基因组调查（Kräyer，1837）

• DOI: 10.6084/m9.figshare.11293922
• 发表时间: 2019
• 作者: Humble J

MOESM5 of Genome-wide survey of cytochrome P450 genes in the salmon louse Lepeophtheirus salmonis (Krøyer, 1837)

MOESM5 对鲑鱼虱子 Lepeophtheirus Salmonis 中的细胞色素 P450 基因进行全基因组调查（Kräyer，1837）

• DOI: 10.6084/m9.figshare.11293931
• 发表时间: 2019
• 作者: Humble J