Giardia are parasitic protozoa whose trophozoite stage infects the upper intestinal tract of humans and of many other vertebrates. G. muris infects rodents and has a similar life cycle as the human pathogen G. duodenalis, therefore providing an excellent model to explore parasite-host interactions in a naturally adapted in vivo system. Giardia species utilize complex cytoskeletal structures to survive in the intestine. In doing so, they use various principles of biomechanics, which we are characterizing in this project. Firstly, to move within the gut and seek for suitable niches, trophozoites swim in the mucus layer of the host, using flagella. We are investigating how the tissue topology and mucus viscosity in the host gut impact on locomotion patterns. Next to host factors, also factors determined by the parasites themselves, such as population density, but also their interference with the host microenvironment, such as mucus viscosity, may influence their motility patterns, points we also will address in our work program. Secondly, to avoid expulsion, trophozoites are equipped with a disc-shaped structure, which they use for attachment to the host intestinal surface. We are analyzing the forces they exert by attaching to host cells and aim to further define the biomechanical properties and functions of the structures forming the parasite-host interface. One focus is on a stamp-like protrusion of the parasite cytoplasm, which moves into the space covered by the adhesive disc. We aim to determine whether this is necessary for more robust adhesion or whether the parasite uses this additional contact area to access nutrients from the host cell. Furthermore, we aim to determine whether G. muris uses additional strategies to resist the forces created by the flow of mucus present in the intestine. Finally, we are investigating if forces exerted by G. muris impact on the host cells. We are investigating how mechanosensors expressed by the cells in contact with the parasite sense and transmit the mecanostimulation. It is important to analyze these principles in an in vivo context wherever possible, as in vitro systems may not naturally reflect the host-parasite interaction. In the first funding period of the SPP2332, we have established unique experimental systems to analyze biomechanical properties of G. muris in their natural habitat, the mouse intestine. We will combine those functional intravital imaging analyses with reductionist in vitro approaches that are available in the consortium, in an iterative approach. This allows us to validate findings from in vitro studies in the natural microenvironment of the parasites.
DFG Programme
Priority Programmes
International Connection
USA
