Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Gate for Bacterial Toxins Found


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 cell of the host absorbs the clostridium perfringens toxin TpeL via the receptor LRP1. The toxins then destroy the cell from within. (left: cell culture without toxins; right: cell culture after toxins were applied). Source: Panagiotis Papatheodorou

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.

Original publication:
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
Further information:

Further reports about: Clostridium PNAS Panagiotis Toxicology bacterium diseases explains genes poisoning procedure proteins receptor toxins

More articles from Life Sciences:

nachricht Tissue-engineered colon from human cells develop different types of neurons
02.10.2015 | Children's Hospital Los Angeles

nachricht Big eyes! – MDC Researchers Identify Cause of Inherited Form of Extreme Nearsightedness
02.10.2015 | Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtz-Gemeinschaft

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: New Sinumerik features improve productivity and precision

EMO 2015, Hall 3, Booth E06/F03

  • Drive optimization called automatically by the part program boosts productivity
  • Automatically switching the dynamic values to rapid traverse and interpolation...

Im Focus: LZH presents additive manufacturing at the LABVOLUTION

The Laser Zentrum Hannover e.V. (LZH) will present how laser-based technologies can contribute to the laboratory of the future at the LABVOLUTION in Hannover in Hall 9, Stand E67/09, from October 6th to 8th, 2015. As a part of the model lab smartLAB, the LZH is showing how additive manufacturing, better known as 3-D printing, can make experimental setups more flexible.

Twelve partners from science and industry are presenting an intelligent and innovative model lab at the special display smartLAB. A part of this intelligent...

Im Focus: New polymer creates safer fuels

Before embarking on a transcontinental journey, jet airplanes fill up with tens of thousands of gallons of fuel. In the event of a crash, such large quantities of fuel increase the severity of an explosion upon impact.

Researchers at Caltech and JPL have discovered a polymeric fuel additive that can reduce the intensity of postimpact explosions that occur during accidents and...

Im Focus: 3-D printing techniques help surgeons carve new ears

When surgical residents need to practice a complicated procedure to fashion a new ear for children without one, they typically get a bar of soap, carrot or an apple.

To treat children with a missing or under-developed ear, experienced surgeons harvest pieces of rib cartilage from the child and carve them into the framework...

Im Focus: Walk the line

NASA studies physical performance after spaceflight

Walking an obstacle course on Earth is relatively easy. Walking an obstacle course on Earth after being in space for six months is not quite as simple. The...

All Focus news of the innovation-report >>>



Event News

EHFG 2015: Securing healthcare and sustainably strengthening healthcare systems

01.10.2015 | Event News

Conference in Brussels: Tracking and Tracing the Smallest Marine Life Forms

30.09.2015 | Event News

World Alzheimer`s Day – Professor Willnow: Clearer Insights into the Development of the Disease

17.09.2015 | Event News

Latest News

Infrared thermography can detect joint inflammation and help improving work ergonomics

02.10.2015 | Medical Engineering

Semiconductor nanoparticles show high luminescence in a polymer matrix

02.10.2015 | Materials Sciences

New Sinumerik features improve productivity and precision

02.10.2015 | Trade Fair News

More VideoLinks >>>