Discussion

The liver fluke, Fasciola hepatica is an economically important trematode pathogen of livestock worldwide and is regarded by the WHO as a re-emerging zoonosis. Predictions indicate and increased prevalence of F. hepatica infection, which is likely to exacerbate its impact on livestock production and human health in future. Control of F. hepatica relies heavily on drug treatment, in particular the drug triclabendazole (TCBZ), which targets the highly pathogenic juvenile fluke migrating through the liver. As with many helminth parasites drug resistance has emerged and poses a substantial threat to sustainable liver fluke control.

This paper will report a series of studies we have taken to define the genetic basis of TCBZ resistance in F. hepatica. We have characterised clonal parental lines of TCBZ-resistant (TCBZ-R) and TCBZ-susceptible (TCBZ-S) liver fluke. In order to identify areas of the genome with signatures of drug selection we have crossed TCBZ-S and TCBZ-R clones and carried out whole-genome mapping of TCBZ-R genes through subsequent F1 and F2 populations. By comparing the frequency of SNP alleles derived from the resistant parental clone and linked to the TCBZ resistance loci in pooled, phenotyped F2 recombinants we have localised a single genomic locus under selection, containing around 30 genes. Recently, we have complemented these mapping studies with metabolomic analysis of TCBZ-R and –S parasites with and without exposure to triclabendazole, in vivo