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

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
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Source:Ecole Polytechnique F茅d茅rale de Lausanne


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