A research team at the Biozentrum of the University of Basel has discovered an protein family that plays a central role in the fight against the bacterial pathogen Salmonella within the cells. The so called interferon-induced GTPases reveal and eliminate the bacterium’s camouflage in the cell, enabling the cell to recognize the pathogen and to render it innocuous. The findings are published in the current issue of the science magazine “Nature”.
Bacteria have developed countless strategies to hide themselves in order to evade attack by the immune system. In the body, Salmonella bacteria use macrophages as host cells to ensure their survival and to be able to spread within the body.
GTPases (green) attack Salmonella typhimurium (red).
(Figure: University of Basel, Biozentrum)
Their survival strategy is to nestle into a vacuole within the cytoplasm of a macrophage, hiding there and multiplying. While they are hidden there, the immune cells cannot detect the bacteria and fight them.
The macrophages, in which the Salmonella hide, however, have also developed a strategy to unmask the disguise of the bacterium and uncover its hiding place. Prof. Petr Broz’s research group at the Biozentrum of the University of Basel has discovered a protein family called interferon-induced GTPases in host cells invaded by Salmonella.
“They are responsible for destroying the hiding place of the pathogen and to initiate the immune response of the cell,” explains Etienne Meunier, first author of the publication.
Once the hiding place has been discovered, GTPases are transported to the vacuole and destabilize its membrane. The bacteria are left behind unprotected in the cytoplasm where their surface molecules are easily recognized by the intracellular defense.
“The GTPases are the key to the hiding place of the bacteria. Once the door has been opened and the protective vacuole destroyed, there is no escape. The bacteria are immediately exposed to the defense machinery of the cell”, says Meunier. Receptors in the cell identify the pathogen, which then activate special cellular enzymes to destroy the bacteria. In addition, the cells own proteases, so-called caspases, are activated and trigger cell death of the infected host cell.
Salmonella still remain a feared pathogenic agent, as they can cause life threatening diarrheal disease. The findings of Broz and his team enable the better understanding of the strategies of the immune cells and to perhaps model this in the future.
The deeper understanding of the immune response of our cells also paves the way for new approaches in using drugs to support the body’s fight against pathogens. In order to further elucidate the mechanisms of the immune response to Salmonella infections, the research team plans to investigate how cells detect the hiding place of the bacteria, the vacuole in the cytoplasm of the macrophages, and what initiates the recruitment of GTPases to the vacuole.
Etienne Meunier, Mathias S. Dick, Roland F. Dreier, Nura Schürmann, Daniela Kenzelmann Broz, Søren Warming, Merone Roose-Girma, Dirk Bumann, Nobuhiko Kayagaki, Kiyoshi Takeda, Masahiro Yamamoto and Petr Broz
Caspase-11 activation requires lysis of pathogen-containing vacuoles by IFN-induced GTPases
Nature (2014); Advance Online Publication | doi: 10.1038/nature13157
Prof. Petr Broz, University of Basel, Biozentrum, phone: +41 61 267 23 42, email: email@example.com
Heike Sacher | Universität Basel
International team discovers novel Alzheimer's disease risk gene among Icelanders
24.10.2016 | Baylor College of Medicine
New bacteria groups, and stunning diversity, discovered underground
24.10.2016 | DOE/Lawrence Berkeley National Laboratory
Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.
"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...
In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.
A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...
By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.
"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...
COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.
In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...
'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.
Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...
14.10.2016 | Event News
14.10.2016 | Event News
12.10.2016 | Event News
24.10.2016 | Power and Electrical Engineering
24.10.2016 | Life Sciences
24.10.2016 | Life Sciences