Alteration of epithelial cell lysosomal integrity induced by bacterial cholesterol-dependent cytolysins.
2017
Malet, Julien Karim | Cossart, Pascale | Ribet, David | Interactions Bactéries-Cellules (UIBC) ; Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM) | Institut Pasteur, INSERM, INRA, National Research Agency, Grant/Award Number: (ANR; ERANET Infect‐ERA PROANTILIS ANR‐13‐IFEC‐0004‐02). French Government’s Investissement d’Avenir program, Laboratoire d’Excellence “Integrative Biology of Emerging Infectious Diseases”, Grant/Award Number: (ANR‐10‐LABX‐62‐IBEID). European Research Council (ERC), Grant/Award Number: (Advanced Grant #233348 MODELIST, H2020‐ERC‐2014‐ADG 670823‐BacCellEpi). Fondation Louis‐Jeantet, Fondation le Roch les Mousquetaires. | We thank J. Gruenberg and R. Schekman for the helpful discussion, M. Hamon for the help with flow cytometry experiments, J. J. Quereda for the construction of the Listeria EGD Δhly strain and F. Stavru for the construction of the GFP-tagged Listeria EGD Δhly strain. | ANR-13-IFEC-0004,PROANTILIS,Subversive pro- and anti-inflammation trade-offs promote infection by Listeria monocytogenes(2013) | ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010) | European Project: 233348,EC:FP7:ERC,ERC-2008-AdG,MODELIST(2009) | European Project: 670823,H2020,ERC-2014-ADG,BacCellEpi(2015)
International audience
اظهر المزيد [+] اقل [-]إنجليزي. 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.
اظهر المزيد [+] اقل [-]المعلومات البيبليوغرافية
تم تزويد هذا السجل من قبل Institut national de la recherche agronomique