Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Bacterial toxin sets the course for infection

08.11.2013
Scientists unravel the role of a pathogen molecule

Every year gastro-intestinal diseases have lethal consequences for more than five million individuals. Researchers from Braunschweig have now discovered what makes a specific strain of Yersinia pseudotuberculosis–one of the main instigators for these infections–so dangerous: the bacteria produce a molecule called CNFy that facilitates the infection process for them.


Yersinia (in blue) cause serious infections.
HZI/Manfred Rohde

It changes the host cells in a manner that enables the injection apparatus of Yersinia, which injects toxins into the cells, to work more efficiently. This strengthens the infection and leads to inflammation of the tissue.

Whether an immune cell divides, alarms other immune cells or dies is strictly controlled in our immune system. “Molecular switches” influence these processes and basically set the course for different pathways. In light of the evolutionary competition between the immune system and the microbes, researchers have found that bacteria produce different substances to manipulate the position of the switches to their advantage.

Scientists at the Helmholtz Centre for Infection Research (HZI) in Braunschweig and at the Hannover Medical School (MHH) have examined one of those substances in more detail. Their results have been published in the American scientific magazine PLOS Pathogens. The team led by Prof Petra Dersch, head of the Department “Molecular Infection Biology”, became aware of the molecule called CNFy, because the bacterium Yersinia pseudotuberculosis produces it in large quantities.

Yersinia pseudotuberculosis is transmitted via contaminated food and can generate gastro-intestinal diseases. However, not all strains produce CNFy. The scientists had therefore assumed that it played no significant role. The interdisciplinary team has now shown that this was a mistake. “Bacteria only produce molecules that are useful for their purposes. Therefore, we wanted to know why Yersinia would need CNFy,” Dersch says.

In order to elucidate its function, the scientists genetically modified a bacterial strain that usually forms CNFy in such a way that it lost the ability to produce this factor. “The altered bacterium was no longer capable of escaping the immune system of the host organism and could not cause disease,” reports Janina Schweer, PhD student at the HZI. This is remarkable since the bacteria certainly have other pathogenic characteristics in their repertoire. They have large molecular complexes at their disposal with which they can inject destructive substances into the host cell. This is a very effective method to promote an infection. “It seems that this mechanism is not sufficiently active in some Yersinia. Apparently, the examined Yersinia strain needs CNFy so that its “molecular syringes” can inject sufficient quantities of active substances into the immune cells,” explains Prof Jochen Hühn, head of the Department “Experimental Immunology” at the HZI. These active substances, mostly cell toxins, damage the immune cells. Many of the substances cause cell mortality. This facilitates the expansion of Yersinia within the infected organism. During advanced infections, inflammation occurs, as well as damage to the tissue.

The researchers have also identified the molecular target that CNFy manipulates, generating the dramatic consequences: this involves the so-called small Rho GTPases. These enzymes initiate a whole cascade of events, for example alteration of the cytoskeleton. This leads to pores in the host cell surface, through which bacterial syringes can more efficiently transport active agents into the cell. The observed cell mortality of the immune cells is introduced through Rho GTPases as well.

“We here have discovered a very clever strategy of Yersinia pseudotuberculosis. With the aid of CNFy, the bacterium manipulates the host cell in such a manner that the injection apparatus can work more effectively,” explains Dersch. “It sets the course for an efficient infection and triggers onset of the disease.”

The present study shows that CNFy is very important for Yersinia. At the same time, it emphasizes the central role of the injection apparatus that is deployed in a more robust manner via CNFy – it is, and remains, an important drug target for intervention measures.

Original publication:
Janina Schweer, Devesha Kulkarni, Annika Kochut, Jörn Pezoldt, Fabio Pisano, Marina C. Pils, Harald Genth, Jochen Hühn und Petra Dersch
The cytotoxic necrotizing factor of Yersinia pseudotuberculosis (CNFy) enhances inflammation and Yop delivery during infection by activation of Rho GTPases.

PLOS Pathogens, 2013

Gastrointestinal infections trigger a wide range of intestinal disorders. They are caused by bacteria such as Yersinia. The Department “Molecular Infection Biology” studies how Yersinia attaches to the intestinal cell layer, prevents attacks of the immune system and spreads within the body.

The Department “Experimental Immunology“ at the HZI studies the development of immune cells and the cellular and molecular mechanisms that keep the immune system in balance. The scientists pay particular attention to the so-called regulatory T cells.

The Helmholtz Centre for Infection Research (HZI)
Scientists at the Helmholtz Centre for Infection Research in Braunschweig, Germany, are engaged in the study of different mechanisms of infection and of the body’s response to infection. Helping to improve the scientific community’s understanding of a given bacterium’s or virus’ pathogenicity is key to developing effective new treatments and vaccines.

http://www.helmholtz-hzi.de

Dr. Birgit Manno | Helmholtz-Zentrum
Further information:
http://www.helmholtz-hzi.de
http://www.helmholtz-hzi.de/en/news_events/news/view/article/complete/bacterial_toxin_sets_the_course_for_infection/

More articles from Life Sciences:

nachricht Two Group A Streptococcus genes linked to 'flesh-eating' bacterial infections
25.09.2017 | University of Maryland

nachricht Rainbow colors reveal cell history: Uncovering β-cell heterogeneity
22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: LaserTAB: More efficient and precise contacts thanks to human-robot collaboration

At the productronica trade fair in Munich this November, the Fraunhofer Institute for Laser Technology ILT will be presenting Laser-Based Tape-Automated Bonding, LaserTAB for short. The experts from Aachen will be demonstrating how new battery cells and power electronics can be micro-welded more efficiently and precisely than ever before thanks to new optics and robot support.

Fraunhofer ILT from Aachen relies on a clever combination of robotics and a laser scanner with new optics as well as process monitoring, which it has developed...

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Fraunhofer ISE Pushes World Record for Multicrystalline Silicon Solar Cells to 22.3 Percent

25.09.2017 | Power and Electrical Engineering

Usher syndrome: Gene therapy restores hearing and balance

25.09.2017 | Health and Medicine

An international team of physicists a coherent amplification effect in laser excited dielectrics

25.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>