Authors

Discussion

Fascioliasis is a disease caused by Fasciola hepatica, affecting both livestock and humans, which poses a substantial threat to food security and human health. The control and management of F. hepatica relies heavily on triclabendazole (TCBZ) due to the absence of vaccines. Over-dependence on TCBZ for fascioliasis control has led to the emergence of TCBZ-resistant F. hepatica strains. Further complications arise from limited diagnostics, making it challenging to differentiate between resistant and susceptible liver fluke infection. Recent work has identified a major locus and the gene content likely responsible for conferring TCBZ resistance. Consequently, there is a pressing need to further confirm potential TCBZ resistance targets, particularly at the protein level. This study aims to utilize an in-depth proteomic approach to confirm the protein profiles from isolates of F. hepatica varying in their TCBZ susceptibility. Proteomic profiles were generated from somatic cells and the secretome (encompassing extracellular vesicles and free excretory-secretory proteins) of four F. hepatica isolates; comprising two TCBZ susceptible (Aberystwyth and Italian) and two TCBZ resistant (Penrith and Kilmarnock). A GeLC approach (1-D SDS PAGE fractionation prior to mass spectrometry) was conducted on somatic and secretome proteins to provide an in-depth proteome profile. The somatic proteomic profile revealed 1236 proteins from all isolates with high confidence hits. Additionally, 312 proteins were identified from extracellular vesicles having high confidence hits. Within these identifications 8 were identified from 30 proteins that maybe likely for conferring TCBZ resistance. Importantly, the proteomes resolved can successfully delineate TCBZ resistant isolates from TCBZ susceptible isolates.