Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Gate for Bacterial Toxins Found

16.04.2014

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 

Contact:
Prof. Dr. Dr. Klaus Aktories
Institute of Experimental and Clinical Pharmacology and Toxicology
University of Freiburg
Phone: +49 (0)761/203-5308
E-Mail: klaus.aktories@pharmakol.uni-freiburg.de

Prof. Dr. Dr. Klaus Aktories | University of Freiburg
Further information:
http://www.uni-freiburg.de

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

More articles from Life Sciences:

nachricht Gene switch may repair DNA and prevent cancer
12.02.2016 | Institute for Integrated Cell-Material Sciences at Kyoto University

nachricht New method opens crystal clear views of biomolecules
11.02.2016 | Deutsches Elektronen-Synchrotron DESY

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Production of an AIDS vaccine in algae

Today, plants and microorganisms are heavily used for the production of medicinal products. The production of biopharmaceuticals in plants, also referred to as “Molecular Pharming”, represents a continuously growing field of plant biotechnology. Preferred host organisms include yeast and crop plants, such as maize and potato – plants with high demands. With the help of a special algal strain, the research team of Prof. Ralph Bock at the Max Planck Institute of Molecular Plant Physiology in Potsdam strives to develop a more efficient and resource-saving system for the production of medicines and vaccines. They tested its practicality by synthesizing a component of a potential AIDS vaccine.

The use of plants and microorganisms to produce pharmaceuticals is nothing new. In 1982, bacteria were genetically modified to produce human insulin, a drug...

Im Focus: The most accurate optical single-ion clock worldwide

Atomic clock experts from the Physikalisch-Technische Bundesanstalt (PTB) are the first research group in the world to have built an optical single-ion clock which attains an accuracy which had only been predicted theoretically so far. Their optical ytterbium clock achieved a relative systematic measurement uncertainty of 3 E-18. The results have been published in the current issue of the scientific journal "Physical Review Letters".

Atomic clock experts from the Physikalisch-Technische Bundesanstalt (PTB) are the first research group in the world to have built an optical single-ion clock...

Im Focus: Goodbye ground control: autonomous nanosatellites

The University of Würzburg has two new space projects in the pipeline which are concerned with the observation of planets and autonomous fault correction aboard satellites. The German Federal Ministry of Economic Affairs and Energy funds the projects with around 1.6 million euros.

Detecting tornadoes that sweep across Mars. Discovering meteors that fall to Earth. Investigating strange lightning that flashes from Earth's atmosphere into...

Im Focus: Flow phenomena on solid surfaces: Physicists highlight key role played by boundary layer velocity

Physicists from Saarland University and the ESPCI in Paris have shown how liquids on solid surfaces can be made to slide over the surface a bit like a bobsleigh on ice. The key is to apply a coating at the boundary between the liquid and the surface that induces the liquid to slip. This results in an increase in the average flow velocity of the liquid and its throughput. This was demonstrated by studying the behaviour of droplets on surfaces with different coatings as they evolved into the equilibrium state. The results could prove useful in optimizing industrial processes, such as the extrusion of plastics.

The study has been published in the respected academic journal PNAS (Proceedings of the National Academy of Sciences of the United States of America).

Im Focus: New study: How stable is the West Antarctic Ice Sheet?

Exceeding critical temperature limits in the Southern Ocean may cause the collapse of ice sheets and a sharp rise in sea levels

A future warming of the Southern Ocean caused by rising greenhouse gas concentrations in the atmosphere may severely disrupt the stability of the West...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Symposium on Climate Change Adaptation in Africa 2016

12.02.2016 | Event News

Travel grants available: Meet the world’s most proficient mathematicians and computer scientists

09.02.2016 | Event News

AKL’16: Experience Laser Technology Live in Europe´s Largest Laser Application Center!

02.02.2016 | Event News

 
Latest News

LIGO confirms RIT's breakthrough prediction of gravitational waves

12.02.2016 | Physics and Astronomy

Gene switch may repair DNA and prevent cancer

12.02.2016 | Life Sciences

Using 'Pacemakers' in spinal cord injuries

12.02.2016 | Medical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>