Gruppe Lundström-Stadelmann

Host-pathogen interactions and drug treatment

 

The pathogen

Within our group we focus on the cestode parasite Echinococcus multilocularis, the fox tapeworm, as a model for multicellular pathogens. E. multilocularis grows like a malignant tumor in its intermediate hosts (mainly rodents, but accidentally also dogs, humans, primates, etc) and thereby causes the disease alveolar echinococcosis. If not treated, parasite growth of this most deadly of all helminth infections leads unequivocally to death of the patient.

 

InVitro
©VONSCHUBERTPHOTO

Project: Novel treatment options against alveolar echinococcosis

performed in collaboration with Prof. Dr. A. Hemphill

Background:
The only curative treatment for AE is surgical resection of the parasite tissue. Surgery is done in about 30% of all AE patients, while most receive chemotherapy only, based solely on the benzimidazole-derivatives mebendazole and albendazole. The present benzimidazole-based chemotherapy cannot kill the parasite (acts only parasitostatic) and therefore has to be taken life-long to avoid parasite regrowth. About 16 % of the treated patients experience adverse effects such as hepatotoxicity that lead to treatment-discontinuation. With increasing numbers of patients and no alternative to benzimidazoles developed so far, it is important to develop better treatment options.

Our aims:
Based on the in vitro cultivation of E. multilocularis, we have developed a number of drug screening assays that allow us to assess larger panels of compounds for activity against E. multilocularis. We are aiming to identify substances that, in contrast to the current therapy, act parasiticidal. We largely focus on already existing drugs or compound classes from other research areas that could be repurposed for the treatment of alveolar echinococcosis. In addition, we want to understand the mechanisms of how certain drugs act on the parasite.

 

Starving deadly pathogens: the metabolism of the cestodes parasite Echinococcus multilocularis and its effects on host cells

Background:
For many pathogens it is yet not completely clear why and how they cause disease and therapies are still often based on broad-spectrum anti-infective drugs rather than on species-specific compounds. Importantly, infectious organisms are dependent on their hosts and the nutrients provided by them. By consumption of host nutrients and metabolites, pathogens can damage their host (and cause pathogenicity) and this in turn induces changes in the host cell and pathogen metabolism. This is also highly interesting with the thought of developing new therapies against pathogens, namely by starving them of essential metabolites.

Our aims:
For a better understanding of the pathogenicity related to E. multilocularis infections, we study the metabolic changes at the host-pathogen interface based on metabolomic and proteomic approaches. This will allow us to study the effects metabolite/protein release/consumption of the parasite has on host cells. Furthermore, the identification of crucial small metabolites and proteins that are released/consumed by E. multilocularis could open up new avenues for the development of alternative or supplementary treatment strategies.

On the left: Schematic representation of the in vitro culture system that lays the basis for our studies. On the right: photography of in vitro cultured E. multilocularis metacestode vesicles.