New-born piglets mostly die painfully from infection caused by an intestinal bacterium. A research team from three faculties at the University of Bern has recently identified the reason behind the fatal intestinal bleeding caused by the bacterium, making a major breakthrough in veterinary research.
Professor Dr Horst Posthaus, Institute of Animal Pathology (ITPA), University of Bern. Image Credit: © Conrad von Schubert.
This breakthrough has also opened up potential opportunities for the development of medications and vaccinations for use in humans.
The Clostridium perfringens bacterium belongs to the large Clostridium genus, which is known to cause various fatal illnesses in humans and animals. Clostridium infections occur extensively.
These bacteria are harmful since they create very strong toxins or poisons that cause targeted damage to the cells of the host. Fatal diseases caused by Clostridium include gas gangrene, tetanus, botulism, and intestinal infections, for instance.
Horst Posthaus’ research team from the University of Bern’s Institute of Animal Pathology is studying an intestinal infection in pigs caused by Clostridium perfringens. A decade ago, the researchers already showed that the toxin generated by the bacteria, the supposed beta toxin, destroys the vascular cells and thus causes bleeding in the intestine of the piglet.
But to date, it was not clear why the toxin particularly attacked these cells and not others. Now, Julia Bruggisser—a doctoral student and biochemist at the Institute of Animal Pathology—has effectively resolved this mechanism through an interdisciplinary association between three faculties. The study findings have been published in Cell Host & Microbe—a specialist journal.
A key molecule
About five years ago, Marianne Wyder, a laboratory technician from the Institute of Animal Pathology, identified a molecule known as Platelet-Endothelial Cell Adhesion Molecule-1—PECAM-1 or even CD31 for short. This molecule is situated on the surface of numerous cells and plays a vital role in piglets’ intestinal bleeding.
The main function of the CD31 molecule is to control the interaction between the blood vessels and inflammatory cells. It mainly occurs on cells that are situated on the inside of blood vessels—the supposed endothelial cells.
During their experiments, the researchers observed that the CD31 molecule and the beta toxin are distributed virtually identically on these cells.
Our project resulted from this initial observation.”
Dr Horst Posthaus, Institute of Animal Pathology, University of Bern
Julia Bruggisser from the Institute of Animal Pathology observed that a toxin discharged by the bacteria in the intestine adheres to the CD31 molecule. Since the beta toxin numbers among the pore-forming toxins, it thus penetrates the cell membrane and destroys the endothelial cells. This causes damage to the vessels and leads to intestinal bleeding.
Researchers at the University of Bern join forces
Researchers from the University of Bern collaborated with multiple other research groups, which was essential for the successful outcome of the project.
Bruggisser stated, “For my research, I work in three laboratories at the university. Although it’s challenging, I learn a lot and above all, its fun.”
Apart from animal pathology, Bruggisser also works with teams led by Britta Engelhardt from Theodor-Kocher Institute, and Christoph von Ballmoos from the Department of Chemistry and Biochemistry.
They had the right questions and ideas. We were able to bring our know-how concerning CD31 and methods and reagents which we had developed into the study," says Britta Engelhardt. "It came together perfectly.”
Christoph von Ballmoos, Department of Chemistry and Biochemistry, University of Bern
Better prophylaxis and medications
The finding makes it feasible to create better vaccines to prevent fatal diseases in pigs.
But we also want to investigate whether the attachment of beta toxin to CD31 on the endothelial cells also allows for the development of new forms of therapy, for vascular disease in humans, for example. We have already started more collaborations within the University of Bern to this end.”
Horst Posthaus, Institute of Animal Pathology, University of Bern
Bruggisser, J., et al. (2020) CD31 (PECAM-1) Serves as the Endothelial Cell-Specific Receptor of Clostridium perfringens β-Toxin. Cell Host & Microbe. doi.org/10.1016/j.chom.2020.05.003.