Newborn piglets may die painfully from infection with the intestinal bacterium Clostridium perfringens, but now, a team of researchers from three faculties at the University of Bern in Switzerland has discovered how the bacterium causes fatal intestinal bleeding.
The breakthrough opens up promising prospects for vaccinations and medications for use in pigs as well as people, the university said in an announcement.
C. perfringens is part of the large Clostridium genus that can cause various fatal illnesses in animals and humans. Clostridium infections are widespread. These bacteria are dangerous because they produce extremely strong poisons (toxins) that cause targeted damage to the host's cells. Dreaded diseases caused by clostridium include botulism, tetanus, gas gangrene and intestinal infections, for example.
Horst Posthaus's group in the Institute of Animal Pathology at the University of Bern is researching an intestinal infection in pigs caused by C. perfringens. They were able to demonstrate 10 years ago that the toxin produced by the bacteria, the so-called beta toxin, kills vascular cells and, thus, causes bleeding in the piglet's intestine. Until now, however, it was unclear why the toxin attacked specifically these cells and not others, the announcement said.
Julia Bruggisser, biochemist and doctoral student at the Institute of Animal Pathology, has succeeded in solving the puzzle of this mechanism in an interdisciplinary collaboration among the three faculties. The findings from the study have been published in the journal Cell Host & Microbe.
Around five years ago, lab technician Marianne Wyder from the Institute of Animal Pathology came across a molecule called Platelet-Endothelial Cell Adhesion Molecule-1 (PECAM-1 or CD31). It is located on the surface of various cells and plays a central role in intestinal bleeding in piglets, the university said.
The actual role of the CD31 molecule is to regulate the interaction between inflammatory cells and blood vessels. It predominantly occurs on cells that are located on the inside of blood vessels (so-called endothelial cells).
During experiments, it was noticed that CD31 and the beta toxin are distributed almost identically on these cells.
"Our project resulted from this initial observation," Posthaus said.
Bruggisser discovered that the toxin released by the bacteria in the intestines attaches to CD31. Since the beta toxin numbers among the pore-forming toxins, it perforates the cell membrane and kills the endothelial cells, which results in damage to the vessels and bleeding in the intestines, the researchers said.
Collaboration among the multiple research groups at the University of Bern was essential for the success of the project. "For my research, I work in three laboratories at the university. Although it's challenging, I learn a lot, and above all, it's fun," Bruggisser said. In addition to animal pathology, she also works with groups headed by Britta Engelhardt with the Theodor-Kocher Institute and Christoph von Ballmoos with the university's 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," Engelhardt said.
Better prophylaxis and medications
The discovery makes it possible to develop better vaccines in order to prevent the fatal disease in pigs, the researchers said.
"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," Posthaus said.
This study was supported by the Swiss National Science Foundation and by a grant for international students at the University of Bern.