The discovery of this pathway, published in the September 22 issue of the journal Cell, advances our understanding of how cells mount a survival response when attacked by bacteria and parasites and also gives insight into the more general process of cell membrane biogenesis.
Bacteria and parasites often use special toxins to perforate the membranes of target cells. These pore-forming toxins are a key weapon in the attack arsenal of some common and virulent bacteria, such as Staphylococcus aureus, well-known for its role in hospital-acquired infections, Streptococcus pneumonie, responsible for middle ear infections and pneumonia, and Helicobacter pylori, implicated in ulcers. Pore-forming toxins compose about a quarter of all known protein toxins that increase the infectivity and severity of bacterial diseases.
Once the toxin perforates the host membrane, ions begin to leak out of the cell. Sensing a drop in its potassium concentration, the cell reacts by forming a multi-protein complex known as an inflammasome. Scientists know that inflammasomes act like a sort of roving security force inside the cell, detecting a variety of danger signals such as bacterial RNA or bits of bacterial flagellin. The inflammasomes join together and activate a protein, caspase-1, that in turn triggers an inflammatory response.
Van der Goot and her colleagues found that in addition to its normal role as a signal for inflammatory response, caspase-1 also triggers the cell’s central regulators for membrane synthesis, launching a bout of lipid metabolism. This previously undetected part of the response pathway has important implications for cell survival.
The Swiss team studied the pathway by using RNA interference to silence genes involved. Interrupting the pathway at any point, either by silencing the genes responsible for the inflammasome formation or the gene for caspase-1, resulted in increased cell death.
“We don’t yet know the details of the mechanism by which lipid metabolism leads to cell survival,” she says. The lipids are probably used to repair the cell membrane, stopping the potassium leak, which itself can kill the cell, and also protecting the cell from additional toxic substances lurking outside.
“This result is important, because it also explains so much in terms of basic cell physiology,” notes Van der Goot. If a cell absorbs too much water, for example, this pathway would be triggered. The lipids formed in the metabolic pathway would enable the cell to enlarge its membrane to accommodate the extra water.
“Toxins have co-evolved with their hosts for a long time,” says Van der Goot. “That makes them good tools with which to study normal cell physiology. This study is a case in point – using a toxin, we have the first step in an understanding of how cells can regulate their membranes in order to maintain a particular ion concentration.”
The research focused on epithelial cells, the cells that line the gut and blood vessels. Van der Goot explains that because they form a protective layer, it’s critical for the organism that these cells survive, even if they don’t function correctly. If the cell dies, it leaves the underlying tissue exposed. She hypothesizes that the toxin response pathway may be different for other types of cells. Immune cells, for example, may be better off committing suicide if their membranes are penetrated, because they could become deadly if their function is compromised.
Van der Goot adds that a better understanding of the biochemical pathway that allows epithelial cells to survive an invasion by a pore-forming toxin will prove valuable as biomedical researchers try to develop drugs to fight antibiotic-resistant strains of bacteria that use these toxins as part of their hijacking strategy.
Gisou Van der Goot is a leading professor in EPFL’s newly formed Global Health Institute, a multidisciplinary initiative that brings researchers from biology, chemistry, computer sciences, engineering and medicine together to work on the major infectious threats of our time, at the level of prevention, diagnostics and therapeutics. She is a Howard Hughes International Research Scholar.
Mary Parlange | alfa
Colorectal cancer risk factors decrypted
13.07.2018 | Max-Planck-Institut für Stoffwechselforschung
Algae Have Land Genes
13.07.2018 | Julius-Maximilians-Universität Würzburg
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.
Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
13.07.2018 | Event News
13.07.2018 | Materials Sciences
13.07.2018 | Life Sciences