Freiburg researchers discover a molecule that smuggles toxins from intestinal pathogens into human cells
Prof. Dr. Dr. Klaus Aktories and Dr. Panagiotis Papatheodorou from the Institute of Experimental and Clinical Pharmacology and Toxicology of the University of Freiburg have discovered the receptor responsible for smuggling the toxin of the bacterium Clostridium perfringens into the cell.
The TpeL toxin is formed by C. perfringens, a pathogen that causes gas gangrene and food poisoning. It is very similar to the toxins of many other hospital germs of the genus Clostridium. The toxins bind to surface molecules and creep into the body cell, where they lead to cell death.
“In order to prevent the toxin from entering the cell, it is necessary to find the receptor that serves as the gatekeeper. But the search for this key molecule remained unsuccessful for a long time,” says Aktories, member of the Cluster of Excellence BIOSS Centre for Biological Signalling Studies. In cooperation with colleagues from Düsseldorf, the USA, and the Netherlands, the researchers from Freiburg have now identified a receptor for a clostridial toxin of this type for the first time ever.
Their findings were published in the journal Proceedings of the National Academy of Sciences (PNAS).
Clostridia cause intestinal and wound diseases in humans and animals that are often fatal. “At the moment, infections with the bacterium Clostridium difficile are particularly problematic in hospitals. The diseases tend to appear following treatment with antibiotics and often lead to diarrhea, but also to fatal inflammations of the bowels,” explains Aktories.
The toxins force their way into host cells and deactivate signaling molecules by attaching a sugar molecule to these cellular switches. Once this signaling pathway has been switched off, the cell dies – infested tissue dies off.
In order to find the receptor, the researchers applied a genetic selection procedure, a so-called screening, in which individual genes in cells from human cancer cell lines are turned off at random. This procedure led to the discovery that cells are immune to the TpeL toxin when the gene for the protein LRP1 is switched off on the cell surface.
LRP1, which stands for low density lipoprotein receptor-related protein 1, usually takes in proteins that serve as a means of transport for lipids in the blood. The researchers demonstrate that LRP1 is the long sought-after key molecule: It also regulates the intake of the toxin TpeL.
His team also proposes a new model, explains Aktories: “Our findings indicate that two receptors are involved in the effect of the other sugar-carrying clostridial toxins.” Researchers can use the findings to develop new agents against clostridia. “Our discovery will also provide new impetus for researchers to identify further toxin receptors,” Aktories hopes.
LRP1 is a receptor for Clostridium perfringens TpeL toxin indicating a two-receptor model of clostridial glycosylating toxins. Björn Schorch, Shuo Song, Ferdy R. van Diemen, Hans H. Bock, Petra May, Joachim Herz, Thijn R. Brummelkamp, Panagiotis Papatheodorou, and Klaus Aktories. PNAS 2014; published ahead of print April 15, 2014, doi:10.1073/pnas.1323790111
Prof. Dr. Dr. Klaus Aktories
Institute of Experimental and Clinical Pharmacology and Toxicology
University of Freiburg
Phone: +49 (0)761/203-5308
Prof. Dr. Dr. Klaus Aktories | University of Freiburg
Severity of enzyme deficiency central to favism
26.07.2016 | Universität Zürich
From vision to hand action
26.07.2016 | Deutsches Primatenzentrum GmbH - Leibniz-Institut für Primatenforschung
Transparent electronics devices are present in today’s thin film displays, solar cells, and touchscreens. The future will bring flexible versions of such devices. Their production requires printable materials that are transparent and remain highly conductive even when deformed. Researchers at INM – Leibniz Institute for New Materials have combined a new self-assembling nano ink with an imprint process to create flexible conductive grids with a resolution below one micrometer.
To print the grids, an ink of gold nanowires is applied to a substrate. A structured stamp is pressed on the substrate and forces the ink into a pattern. “The...
A new Fraunhofer MEVIS method conveys medical interrelationships quickly and intuitively with innovative visualization technology
On the monitor, a brain spins slowly and can be examined from every angle. Suddenly, some sections start glowing, first on the side and then the entire back of...
Researchers at the U.S. Department of Energy's (DOE) Ames Laboratory have discovered an unusual property of purple bronze that may point to new ways to achieve high temperature superconductivity.
While studying purple bronze, a molybdenum oxide, researchers discovered an unconventional charge density wave on its surface.
Munich Physicists have developed a novel electron microscope that can visualize electromagnetic fields oscillating at frequencies of billions of cycles per second.
Temporally varying electromagnetic fields are the driving force behind the whole of electronics. Their polarities can change at mind-bogglingly fast rates, and...
Breakup of continents with two speed: Continents initially stretch very slowly along the future splitting zone, but then move apart very quickly before the onset of rupture. The final speed can be up to 20 times faster than in the first, slow extension phase.phases
Present-day continents were shaped hundreds of millions of years ago as the supercontinent Pangaea broke apart. Derived from Pangaea’s main fragments Gondwana...
15.07.2016 | Event News
15.07.2016 | Event News
11.07.2016 | Event News
26.07.2016 | Information Technology
26.07.2016 | Health and Medicine
26.07.2016 | Physics and Astronomy