They identify proteins involved in the development of the parasite responsible for fasciolosis

Fasciolosis is a zoonotic disease caused by the parasite Fasciola hepatica and affects both animals and humans worldwide. Due to its pathogenic nature, this parasitic worm causes major health and economic problems worldwide.

Researchers from the Spanish National Research Council (CSIC) have identified a series of proteins involved in relevant biological processes for the development of Fasciola hepatica. The team is led by the Laboratory of Parasitic Helminths of Zoonotic Importance (ATENEA), of the Institute of Natural Resources and Agrobiology of Salamanca (IRNASA), attached to the CSIC, and has been carried out in collaboration with scientists from the Carlos III Health Institute and the universities of Salamanca and Córdoba, all of these entities in Spain. The discoveries made by this team could help in the identification of new targets for the control and treatment of this disease.

Fasciolosis is caused by ingestion of aquatic plants or water contaminated with their larvae, called metacercariae, which migrate through the host to reach the main bile ducts, where they mature into adult worms.

It affects animals (particularly large herbivorous species such as cattle and sheep) and humans throughout the world, causing significant economic losses for farmers and health problems in developing countries. For this reason, it has the status of a neglected disease, being included in the group of infectious diseases that mainly affect the poorest populations and those with limited access to health services.

Microscope image of the parasitic worm Fasciola hepatica. (Photo: IRNASA / CSIC)

As detailed by David Becerro Recio, an IRNASA researcher and co-author of the two recently published studies in this line of research, the treatment and prevention of this disease is a problem of growing concern due to the appearance of parasites resistant to the medicine available in currently, triclabendazole, and to the limited efficacy of the tested vaccines.

It is essential to develop antiparasitic vaccines, diagnostic tests and new drugs for the treatment and prevention of fasciolosis.

With this objective, the team has delved into the infection process by this parasite, specifically, the early interactions between the host and Fasciola hepatica. It has been possible to identify, as Becerro Recio points out, proteins involved in proteolysis or protein degradation, “a fundamental process for the parasite since it allows it to migrate through the host’s tissues, degrade its structures to feed itself and degrade the antibodies that It has “stuck” to its surface as a defense mechanism. Proteins related to the alteration of other processes such as parasite nutrition, the response to free radicals or the parasite’s muscle activity have also been detected.

To characterize the changes that occur in this first interaction, the researchers have developed a new in vitro model that replicates the moment in which the juvenile form of the parasite crosses the intestinal wall of the host. “On the one hand, we have used juveniles of the parasite and, on the other, a culture of primary epithelial cells from the mouse small intestine and we have put them in contact in a plate. After a period of joint incubation, we separate both organisms and perform a protein extraction. And using proteomics and bioinformatics techniques, we determine which proteins change their expression levels after that contact”, says the researcher. On the other hand, the team of scientists has proposed an ex vivo model, a mouse animal model, to determine what effects passage through the intestinal wall has for both organisms.

The molecules identified in these models of early host-parasite interactions could help define new tools against fasciolosis. To this end, IRNASA researchers continue to delve into these processes. “For the moment we have characterized which proteins change their expression, but we also want to analyze, using the same in vitro model, what happens with the RNAs of the cells, to find out if there is a correlation between the proteomic data and at the RNA level, and perform a transcriptomic approach”, advances Becerro Recio.

One of the studies is entitled “Proteomics coupled with in vitro model to study the early crosstalk occurring between newly excysted juveniles of Fasciola hepatica and intestinal host cells”. The other study is entitled “Study of the migration of juvenile Fasciola hepatica across the intestinal barrier of the host by quantitative proteomics in an ex vivo model”. Both have been published in the academic journal PLOS Neglected Tropical Diseases. (Source: IRNASA / CSIC)