Role of P-glycoprotein in emamectin benzoate (SLICE®) resistance in sea lice, Lepeophtheirus salmonis
Role of P-glycoprotein in emamectin benzoate (SLICE®) resistance in sea lice, Lepeophtheirus salmonis
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DOI：
10.1016/j.aquaculture.2012.03.026
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发表时间：
2012-05-21
期刊：
影响因子：
4.5
通讯作者：
Burka, John F.
中科院分区：
文献类型：
--
作者：
Igboeli, Okechukwu O.;Fast, Mark D.;Burka, John F.
甲氨基阿维菌素苯甲酸盐（EMB; SLICE（R））由于其易于给药以及对所有寄生阶段的海虱有效，在过去十年中一直是控制鲑鱼水产养殖中海虱的首选药物。这种过度依赖导致对毒品的耐受性增加，从而减少了毒品的使用。已知ATP结合盒（ABC）转运蛋白如P-糖蛋白（P-gp）参与耐药性。本研究调查了1）EMB与P-gp的相互作用，2）EMB浓度增加对雄性和雌性海虱（Lepeophtheirus salmonis）P-gp mRNA表达的影响，以及3）存档的成年雌性Lepeophtheirus salmonis中转运蛋白mRNA表达的变化。鲑鱼生物测定结果的分析表明，与2002年至2004年进行的类似研究相比，2011年收集的样品的EMB EC 50高出4至26倍，表明EMB对寄生虫的功效丧失。ATP酶活性测定和竞争性抑制试验表明EMB与转运蛋白相互作用。甲氨基阿维菌素苯甲酸盐对寄生虫P-gp mRNA表达具有显著的浓度依赖性影响。从2002年到2011年收集的海虱样本中P-gp mRNA水平有时间上的增加。我们的研究结果表明，EMB是P-gp的底物，该转运蛋白可能参与了杀寄生虫剂在L.鲑鱼(C)2012爱思唯尔有限公司版权所有。
Emamectin benzoate (EMB; SLICE (R)) has been the drug of choice for the control of sea lice in salmon aquaculture within the past decade due to its ease of administration as well as efficacy on all parasitic stages of sea lice. This over-reliance has led to increased tolerance to the drug and a consequent decline in its use. ATP-binding cassette (ABC) transporters such as P-glycoprotein (P-gp) are known to be involved in drug resistance. The present study investigated 1) the interaction of EMB with P-gp, 2) the effect of increasing EMB concentrations on P-gp mRNA expression in male and female sea lice, Lepeophtheirus salmonis, from Atlantic salmon (Salmo salar) farms in the Bay of Fundy, NB, as well as 3) changes in the mRNA expression of the transporter in archived adult female L. salmonis. Analysis of bioassay results indicated a 4 to 26 fold higher EMB EC50 for samples collected in 2011 compared to a similar study carried out between 2002 and 2004 suggesting loss of EMB efficacy in the parasite. An assay for ATPase activity as well as a competitive inhibition test showed that EMB interacts with the transporter. Emamectin benzoate had a significant concentration-dependent effect on P-gp mRNA expression in the parasite. There was a temporal increase in levels of P-gp mRNA in sea lice samples collected from 2002 to 2011. Our results indicate that EMB is a substrate for P-gp and that the transporter could be involved in the loss of efficacy of the parasiticide in L. salmonis. (C) 2012 Elsevier B.V. All rights reserved.