title: Alteration of epithelial cell lysosomal integrity induced by bacterial cholesterol-dependent cytolysins.
abstract: Bacterial pathogens can interfere during infection with host cell organelles, such as mitochondria, the endoplasmic reticulum-Golgi system or nuclei. As important cellular functions are often compartmentalized in these organelles, their targeting allows pathogens to manipulate key host functions during infection. Here, we identify lysosomes as a new class of organelles targeted by the pathogenic bacterium Listeria monocytogenes. We demonstrate that extracellular Listeria, via secretion of the pore-forming toxin listeriolysin O, alters lysosomal integrity in epithelial cells but not in macrophages. Listeriolysin O induces lysosomal membrane permeabilization and release of lysosomal content, such as cathepsins proteases, which remain transiently active in the host cytosol. We furthermore show that other bacterial pore-forming toxins, such as perfringolysin O and pneumolysin, also induce lysosomes alteration. Together, our data unveil a novel activity of bacterial cholesterol-dependent cytolysins.
authors.affiliation: Unité des Interactions Bactéries-Cellules, Institut Pasteur, F-75015, Paris, France.|Inserm, U604, F-75015, Paris, France.|INRA, USC2020, F-75015, Paris, France.|Univ. Paris Diderot, Sorbonne Paris Cité, F-75015, Paris, France.
authors.forename: Julien Karim
authors.initials: JK
authors.lastname: Malet
authors.affiliation: Unité des Interactions Bactéries-Cellules, Institut Pasteur, F-75015, Paris, France.|Inserm, U604, F-75015, Paris, France.|INRA, USC2020, F-75015, Paris, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Cossart
authors.affiliation: Unité des Interactions Bactéries-Cellules, Institut Pasteur, F-75015, Paris, France.|Inserm, U604, F-75015, Paris, France.|INRA, USC2020, F-75015, Paris, France.
authors.forename: David
authors.initials: D
authors.lastname: Ribet
mesh_terms: D000818:Animals; D001427:Bacterial Toxins; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability; D004847:Epithelial Cells / Q000382:microbiology*; D006367:HeLa Cells; D006360:Heat-Shock Proteins / Q000502:physiology*; D006460:Hemolysin Proteins / Q000502:physiology*; D056945:Hep G2 Cells; D006801:Humans; D008089:Listeria monocytogenes / Q000502:physiology*; D008088:Listeriosis / Q000382:microbiology* / Q000473:pathology; D008247:Lysosomes / Q000382:microbiology / Q000502:physiology*; D051379:Mice; D059748:Proteolysis; D000067996:RAW 264.7 Cells
chemical_list: D001427:Bacterial Toxins; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; C038705:hlyA protein, Listeria monocytogenes