Gruppe Posthaus

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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).

Organs from animals
FIG 1: Organs from animals that died of suspected or proven clostridial diseases, taken from our necropsy hall at the Institute of Animal Pathology.

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.

FIG 2: PFT mechanism of action; (A) Secretion as soluble monomer, (B) binding to receptor, (C) oligomerization, and (D) insertion as transmembrane pore. Figure created by Basma Tarek and Julia Bruggisser

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).

Pathogenesis of C. perfringens
Fig 3. Pathogenesis of C. perfringens type C enteritis in pigs. (A) Colonization of small intestine, proliferation of C. perfringens type C, toxin secretion. (B) CPB can pass the epithelial barrier (mechanism unknown) and reaches blood vessels. (C) CPB damages endothelial cells, this releases fluid, plasma proteins and erythrocytes. Potential inhibition of hemostasis (blood clot formation) through CPB by damaging platelets. (D) A vicious cycle of CPB-induced hemorrhage, tissue necrosis, accelerated clostridial growth and toxin secretion develops. (E) Fulminant progression leads to death within hours (F). The subacute stage of the disease with inflammation develops in cases where the initial acute damage was less severe and did not cause immediate death. Figure created by Julia Bruggisser (Posthaus et al, JVDI, 2020).

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).

Fig 4. Role of C. perfringens β-toxin (CPB) in disease
Fig 4. Role of C. perfringens β-toxin (CPB) in disease. CPB kills endothelial cells after binding to its receptor, Platelet-Endothelial Cell Adhesion Molecule 1 (CD31 or PECAM-1), which is present mainly on these cells. Figure created by Julia Bruggisser (Bruggisser et al. Cell Host & Microbe, 2020).

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).

Anticipated Toxin-to-Therapy pipeline
Fig. 5 Anticipated Toxin-to-Therapy pipeline aiming to develop strategies that inhibit bacterial toxin damage in animals and humans. Figure created with

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



ausgewählte Manuskripte aus unserer Forschung

  • Bruggisser, J., Iacovache, I., Musson, S., Degiacomi, M., Posthaus, H., Zuber, B. (2022) Cryo-EM structure of the octameric pore of Clostridium perfringens β-toxin. EMBO Reports
  • Tarek, B., Bruggisser, J., Cattalani, F., Posthaus, H., (2021). Platelet endothelial cell adhesion molecule 1 (CD31) is essential for Clostridium perfringens beta-toxin mediated cytotoxicity in human endothelial and monocytic cells. Toxins 13(12): 893. 
  • Bruggisser, J., Tarek, B., Wyder, M., Witz, G., Enzmann, G., Deutsch, U., Engelhardt, B., Posthaus, H. (2020) CD31 (PECAM-1) serves as the endothelial cell-specific receptor of Clostridium perfringens β-toxin. Cell Host & Microbe 28, 1–10
  • Posthaus, H., Kittl, S., Tarek, B., and Bruggisser, J. (2019) Clostridium perfringens type C enteritis in pigs: diagnosis, pathogenesis, and prevention. Journal of Veterinary Diagnostic Investigation, 2020 32(2):203-212.
  • Richard, O. K., Springer, S., Finzel, J., Theuss, T., Wyder, M., Vidondo, B., and Posthaus, H. (2019) Application of an Endothelial Cell Culture Assay for the Detection of Neutralizing Anti-Clostridium Perfringens Beta-Toxin Antibodies in a Porcine Vaccination Trial. Toxins 11 (4), 225

Eine vollständige Publikationenliste finden Sie unter NCBI.

Marko Jäggi

Julien Miclard

Benno Grabscheid

Corinne Gurtner

Francesca Popescu

Esther Sutter

Katrin Schäfer

Ahmet Candi

Simone Roos

Anne Thiel

David Vazquez

Julia Bruggisser

Marianne Wyder

PhD position in bacterial host-pathogen interaction