Institute of Aquaculture
Resistance may soon become futile Understanding the genetic basis of drug resistance in sea lice SEA lice (family Caligidae) are copepod crustacean ectoparasites of marine fish, which feed on the host’s mucus, blood and skin tissues. Sea lice cause significant impacts globally as pathogens in marine finfish aquaculture, and have proven a particular problem for Atlantic salmon farming. Control of sea lice has traditionally relied on veterinary treatments delivered as medicinal baths or feed additives. In addition, non-medicinal strategies are now widely employed and include biological control using cleaner fish, thermal and freshwater delousing, and modified cage designs reducing infection pressure. Despite the accessibility of these and other new approaches to sea louse control, medicinal treatments still remain essential, as situations can arise where alternative treatment options are unavailable, are only partly successful or are advised against from a veterinary perspective. However, an inherent problem with medicinal approaches is that pests and parasites can evolve resistance against chemical control agents, particularly when the same or similarly acting compounds are used over extended time periods with insufficient rotation with dissimilar products. Resistance against drugs or pesticides is based on the increase, within the pest population, of genetic variants that allow those carrying them to survive treatments. Such genetic variants usually exist already prior to the use of a control agent, but are extremely rare within the population’s gene pool. The use of the same treatment over many generations will tend to selectively remove individuals not carrying the resistance conferring genetic variant, and therefore slowly increase its frequency in the gene pool. Once this process reaches the point where a large proportion of the parasites in a population are carriers of the genetic variants, treatment failures occur and resistance becomes apparent. Only a restricted range of anti-sea louse medicines are licensed for use in the UK. Compounds used in available bath treatments include azamethiphos, deltamethrin and hydrogen peroxide, while emamectin benzoate is used in oral treatments. The success of all the above treatments can be affected by resistance development in the salmon louse, Lepeophtheirus salmonis, the sea louse species most commonly infecting Atlantic salmon, with considerable variation of resistance occurring according to site location and seasonal/inter-annual variability. Despite the high relevance of drug resistance in L. salmonis, comparatively little is known about the molec46
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Opposite: Sea lice on salmon.
ular mechanisms involved. In insects, pesticide resistance is most commonly based on one or both of two major mechanisms. On the one hand, mutations leading to changes in the structure of the pesticide’s molecular target site can disrupt its efficacy. On the other hand, mutations increasing the breakdown of the pesticide through metabolism can enable resistant insects to rid themselves of the pesticide before it can act. In L. salmonis, resistance against azamethiphos is caused by a target site mutation. The mechanisms underlying resistance against other salmon delousing agents are currently unknown. Closing such still existing knowledge gaps with regard to the detailed mechanisms of drug resistance in salmon lice will significantly contribute to combat the aquaculture parasite. Understanding the molecular mechanism of resistance will enable the design of improved medicines capable of breaking the resistance. Moreover, the development of diagnostic tests allowing the detection of resistance in sea louse populations will allow optimising management strategies stopping the spread of resistance and monitor the success of such measures. In the BBSRC-funded research project, Identifying molecular determinants of drug susceptibility in salmon lice (Lepeophtheirus salmonis)’ (BB/L022923/1), also involving the Scottish Salmon Producers’ Organisation (SSPO), the team of Dr Armin Sturm at the University of Stirling’s Institute of Aquaculture have used a genetic approach to obtain insights into the mechanisms of resistance against the bath treatment deltamethrin and the feed additive emamectin benzoate in L. salmonis. In breeding crosses, sea lice from a population resistant against both drugs and those from a drug susceptible population were interbred and the inheritance of resistance followed through the first and second daughter generations. To identify genetic markers within the genome, which are associated with drug resistance, parasites from selected families of the crosses were subjected to high-throughput gene sequencing. The first results, summarised in a publication led by postdoctoral fellow Dr Greta Carmona-Antoñanzas (PLoS ONE, 2017, 12(7): e0180625), revealed an unexpected pattern of inheritance of deltamethrin resistance in L. salmonis. In the families obtained from cross-breeding, all offspring from resistant female parents were resistant. In contrast, whether male parents were resistant or not had only minor effects on the occurrence of deltameInstitute of Aquaculture
08/05/2018 11:06:59