The potential role of ABC transporters as factors influencing drug susceptibility in the salmon louse, Lepeophtheirus salmonis (Kroyer, 1837)

• Main Author: Heumann, Jan H
• Other Authors: MSD Animal Health
• Format: Doctoral or Postdoctoral Thesis
• Language: English
• Published: University of Stirling 2014
• Subjects: sea lice; salmon louse; Lepeophtheirus salmonis; L salmonis; Atlantic salmon; Salmo salar; emamectin benzoate; avermectin; drug resistance; drug susceptibility; ATP-binding cassette transporter; ABC transporter; bioassay; parasite; ectoparasite; copepod; Drug resistance in microorganisms; Fishes Diseases; Canada; Norway
• Online Access: http://hdl.handle.net/1893/21812; http://dspace.stir.ac.uk/bitstream/1893/21812/1/20150529%20Thesis%20FINAL%20VERSION.pdf

Efficient control of sea lice is a major challenge for the sustainable production of farmed Atlantic salmon (Salmo salar (Linnaeus, 1758)). These marine ectoparasites feed on mucus, skin and blood of their hosts, thereby reducing the salmon’s growth rate and overall health. In the northern hemisphere, the most prevalent species is Lepeophtheirus salmonis (Krøyer, 1837). In 2006, global costs of sea lice infections are estimated to have exceeded €300 million, with the majority spent on a limited number of chemical delousing agents. Emamectin benzoate (EMB; SLICE®), an avermectin, has been widely used since its introduction in 2000, due to its convenient administration as an in-feed medication and its high efficacy against all parasitic stages of L. salmonis. However, over-reliance on a single or limited range of medicines favours the emergence of drug resistance and, as a result, the efficacy of this compound in treating L. salmonis has decreased in recent years, as reported from e.g. Chile, Norway, Scotland and Canada. Declining efficacy underlines the need for an improved understanding of the molecular mechanisms underlying EMB drug resistance in L. salmonis. Elucidation of these mechanisms would allow for improved monitoring tools, earlier detection of developing resistance, extended usability of current delousing agents and development of new parasiticides. The work described in this thesis sets out to examine the molecular mechanisms underlying EMB resistance in L. salmonis. In earlier studies, research in nematodes and arthropods has linked drug efflux transporters belonging to the family of ATP-binding cassette (ABC) transporters to ivermectin (IVM) resistance, a parasiticide with high chemical similarity to EMB. ABC transporters such as permeability glycoprotein (P-gp), transport a wide range of substrates, including drugs, and have been suggested to provide a potential molecular mechanism through which EMB resistance might be mediated in sea lice. As an example of such mechanisms, increased expression of ...