Gruppe Posthaus

SNF-Sinergia Projekt DISPERSE

The Posthaus group works on bacterial host-pathogen interaction with a focus on the effect of bacterial pore-forming toxins on host cells. Our research methodology includes in situ investigations in naturally diseased animals, cell- and molecular biology and biochemical tools, genetic modifications of cell lines and others. To extend our methodological spectrum we collaborate with experienced research groups at the University of Bern and outside. Clostridia are dangerous pathogens in animals and humans. At our diagnostic necropsy service in Bern, we regularly diagnose clostridial infections in animals (Fig 1).

Clostridia damage their hosts using potent exotoxins. Pore-forming toxins (PFTs) are the largest group of these. PFTs are secreted by the pathogen as a water soluble monomer that binds to plasma membrane receptors of the target cells (Fig. 2). Here they oligomerize and form a membrane-spanning pore that allows ion efflux/influx and eventually cause cellular responses that can lead to cell death and severe tissue damage.

Among the clostridial PFTs, so called hemolysin βPFTs form the largest class. Currently, 13 of these toxins have been identified, however, a clear role in animal or human disease has so far only been proven for few of them. In addition, currently unidentified PFTs might be involved in clostridial diseases that so far cannot be attributed to particular clostridial toxinotypes. Our group wants to identify and characterize clostridial hemolysin βPFTs that likely play central roles in animal diseases. Over the past decade we contributed significantly to the current understanding of C. perfringens β-toxin's role in necrotic enteritis in animals and humans (Fig. 3).

In 2020, we unraveled the mechanism of target cell specificity of C. perfringens β-toxin by identifying Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1 or CD31) as its cellular receptor (Fig. 4) (Bruggisser et al, Cell Host Microbe, 2020). In collaboration with the Group of Prof. Benoit Zuber at the Institute of Anatomy, Medical School, and Prof. M. Degiacomi (Durham University) we also determined the Cryo-EM structure of the transmembrane β-toxin pore (Bruggisser, Iacovache et al., EMBO Reports, 2022).

Using the β-toxin as the best studied member of the clostridial hemolysin βPFTs, we now continue our structure-function analyses and extend our research to multiple related toxins secreted by C. perfringens. Our long term goal is to contribute to the development of novel strategies directed against these toxins that can be used to prevent or treat clostridial diseases in animals and humans (Fig. 5).

Besides our primary research topic we offer support for research groups at our faculty and outside as part of our COMPATH platform.