title: Pore-forming toxins induce multiple cellular responses promoting survival.
abstract: Pore-forming toxins (PFTs) are secreted proteins that contribute to the virulence of a great variety of bacterial pathogens. They inflict one of the more disastrous damages a target cell can be exposed to: disruption of plasma membrane integrity. Since this is an ancient form of attack, which bears similarities to mechanical membrane damage, cells have evolved response pathways to these perturbations. Here, it is reported that PFTs trigger very diverse yet specific response pathways. Many are triggered by the decrease in cytoplasmic potassium, which thus emerges as a central regulator. Upon plasma membrane damage, cells activate signalling pathways aimed at restoring plasma membrane integrity and ion homeostasis. Interestingly these pathways do not require protein synthesis. Cells also trigger signalling cascades that allow them to enter a quiescent-like state, where minimal energy is consumed while waiting for plasma membrane damage to be repaired. More specifically, protein synthesis is arrested, cytosolic constituents are recycled by autophagy and energy is stored in lipid droplets.
authors.affiliation: Global Health Institute, Ecole Polytechnique Fédérale de Lausanne, Faculty of Life Sciences, Lausanne, Switzerland.
authors.forename: Manuel R
authors.initials: MR
authors.lastname: Gonzalez
authors.forename: Mirko
authors.initials: M
authors.lastname: Bischofberger
authors.forename: Barbara
authors.initials: B
authors.lastname: Frêche
authors.forename: Sylvia
authors.initials: S
authors.lastname: Ho
authors.forename: Robert G
authors.initials: RG
authors.lastname: Parton
authors.forename: F Gisou
authors.initials: FG
authors.lastname: van der Goot
mesh_terms: D001343:Autophagy; D001419:Bacteria / Q000472:pathogenicity*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D004847:Epithelial Cells / Q000382:microbiology* / Q000502:physiology*; D006801:Humans; D050356:Lipid Metabolism; D052899:Pore Forming Cytotoxic Proteins / Q000378:metabolism* / Q000633:toxicity*; D011188:Potassium / Q000378:metabolism; D014176:Protein Biosynthesis; D015398:Signal Transduction; D013312:Stress, Physiological
chemical_list: D052899:Pore Forming Cytotoxic Proteins; D011188:Potassium