Advances in Fasciola hepatica research using ‘omics’ technologies

Abstract

The liver fluke Fasciola hepatica is an economically important pathogen of livestock worldwide, as well as being an important neglected zoonosis. Parasite control is reliant on the use of drugs, particularly triclabendazole, which is effective against multiple parasite stages. However, the spread of parasites resistant to triclabendazole has intensified the pursuit for novel control strategies. Emerging 'omics' technologies are helping advance our understanding of liver fluke biology, specifically the molecules that act at the host-parasite interface and are central to infection, virulence and long-term survival within the definitive host. This review discusses the technological sequencing advances that have facilitated the unbiased analysis of liver fluke biology, resulting in an extensive range of 'omics' datasets. In addition, we highlight the 'omics' studies of host responses to F. hepatica infection that, when combined with the parasite datasets, provide the opportunity for integrated analyses of host-parasite interactions. These extensive datasets will form the foundation for future in-depth analysis of F. hepatica biology and development, and the search for new drug or vaccine interventions.

Fasciola hepatica Extracellular Vesicles isolated from excretory-secretory products using a gravity flow method modulate dendritic cell phenotype and activity

“…Resistance to triclabendazole, the longstanding gold standard chemotherapeutic treatment, means that the development of new chemotherapies [30], or better still, vaccines [24] is critical. Most past research has focused on the molecules associated with the surface tegument and secretome of F. hepatica as the main sources of vaccine candidates [31,32]. However, because of their aforementioned importance in host-parasite interaction, attention is now turning to EVs and their cargo for the discovery of novel therapeutic targets [25,33,34].…”

Fasciola hepatica-Derived Molecules as Regulators of the Host Immune Response

“…Co-evolution of humans and helminths may have shaped the human immune system as helminths developed sophisticated mechanisms to induce tolerance and evade expulsion by the host enabling them to become successful chronic pathogens ( 7 – 9 ). A range of genomic, transcriptomic, immunomic, glycomic, and proteomic approaches alongside database mining has provided further perspective on host-parasite interactions and led to the identification of various helminth molecules including those within excretory-secretory (ES) products that influence the host inflammatory response ( 10 – 15 ). These molecules have garnered much attention with the ultimate aim of exploiting their immunoregulatory mechanisms for the treatment of human diseases ( 16 , 17 ).…”

Comparative Proteomics Analysis of Anisakis simplex s.s.—Evaluation of the Response of Invasive Larvae to Ivermectin

“…Additionally, Fasciola hepatica ’s susceptibility to the anthelminthic drug triclabendazole, characterized by lethal activity, was indicated by the presence of actin, also one of the motor proteins. Moreover, the interaction of filamentous actin with myosin forms the basis of muscle contraction, which, when disrupted or taken over by antiparasitic drugs, might be the cause of parasite death [ 45 , 46 ]. According to the literature data mentioned previously, anthelmintics influence the motor proteins and thus reduce parasite motility, causing death; however, in our case, IVM did not affect the motility and survival of A. simplex s.s., even though the protein level of myosin was modulated.…”

“…Additionally, endopeptidases, like the serine proteases detected in this study, play a significant role in the lifecycle of the parasite and in the pathogen‒host relationship that could be related to virulence, invasion of host tissues, and/or intracellular digestion ( File S2 ) [ 49 , 50 ]. Moreover, the previously mentioned putative resistance of Fasciola hepatica to triclabendazole, characterized by sublethal activity, was indicated by the presence of cathepsin L, a peptidase [ 46 ].…”