Navigation Links
A new understanding of how cells defend themselves against bacterial pore-forming toxins

Biologists at the EPFL (Ecole Polytechnique Federale de Lausanne) have unveiled a new twist in a metabolic pathway that cells use to defend themselves against toxins made by disease-causing bacteria.

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. Interr upting 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 b acteria that use these toxins as part of their hijacking strategy.

Source:Ecole Polytechnique F茅d茅rale de Lausanne

Related biology news :

1. UCSB scientists probe sea floor venting to gain understanding of early life on Earth
2. Zebrafish may hold key to understanding human nerve cell development
3. Novel ultrafast laser detection of cancer cells also may improve understanding of stem cells
4. Researchers make gains in understanding antibiotic resistance
5. Brain-mapping technique aids understanding of sleep, wakefulness
6. New understanding of DNA repair may pave way to cancer treatments
7. NYU and MSKCC research provides model for understanding chemically induced cancer initiation
8. Virologists make major step towards understanding the process of HIV infection
9. New understanding of cell movement may yield ways to brake cancers spread
10. Proteomics brings researchers closer to understanding microbes that produce acid mine drainage
11. New understanding of jet lag

Post Your Comments:

(Date:5/3/2016)... , May 3, 2016  Neurotechnology, a provider ... MegaMatcher Automated Biometric Identification System (ABIS) , ... multi-biometric projects. MegaMatcher ABIS can process multiple complex ... any combination of fingerprint, face or iris biometrics. ... SDK and MegaMatcher Accelerator , which ...
(Date:4/28/2016)... Sweden , April 28, 2016 First ... M (139.9), up 966% compared with the first quarter of 2015 ... profit totaled SEK 589.1 M (loss: 18.8) and the operating margin ... 7.12 (loss: 0.32) Cash flow from operations was SEK ... The 2016 revenue guidance is unchanged, SEK 7,000-8,500 M. ...
(Date:4/26/2016)... Research and Markets has announced ... 2016-2020"  report to their offering.  , ,     (Logo: ... analysts forecast the global multimodal biometrics market to ... period 2016-2020.  Multimodal biometrics is being ... the healthcare, BFSI, transportation, automotive, and government for ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... 2016 Houston Methodist Willowbrook Hospital has ... Association to serve as their official health care ... Willowbrook will provide sponsorship support, athletic training services, ... coaches, volunteers, athletes and families. "We ... Association and to bring Houston Methodist quality services ...
(Date:6/23/2016)... ... 23, 2016 , ... Supplyframe, the Industry Network for electronics ... Lab . Located in Pasadena, Calif., the Design Lab’s mission is to bring ... designed, built and brought to market. , The Design Lab is Supplyframe’s physical ...
(Date:6/23/2016)... LONDON , June 23, 2016 ... & Hematology Review, 2016;12(1):22-8 ... Review , the peer-reviewed journal from touchONCOLOGY, ... the escalating cost of cancer care is placing ... a result of expensive biologic therapies. With the ...
(Date:6/23/2016)...  Amgen (NASDAQ: AMGN ) today announced ... life sciences incubator to accelerate the development of new ... at QB3@953 was created to help high-potential life science ... early stage organizations - access to laboratory infrastructure. ... two "Amgen Golden Ticket" awards, providing each winner with ...
Breaking Biology Technology: