title: Listeria monocytogenes dampens the DNA damage response.
abstract: The DNA damage response (DDR) is an essential signaling pathway that detects DNA lesions, which constantly occur upon either endogenous or exogenous assaults, and maintains genetic integrity. An infection by an invading pathogen is one such assault, but how bacteria impact the cellular DDR is poorly documented. Here, we report that infection with Listeria monocytogenes induces host DNA breaks. Strikingly, the signature response to these breaks is only moderately activated. We uncover the role of the listerial toxin listeriolysin O (LLO) in blocking the signaling response to DNA breaks through degradation of the sensor Mre11. Knocking out or inactivating proteins involved in the DDR promotes bacterial replication showing the importance of this mechanism for the control of infection. Together, our data highlight that bacterial dampening of the DDR is critical for a successful listerial infection.
authors.affiliation: Institut Pasteur, Unité des interactions Bactéries-Cellules, Paris, France; The French National Institute of Health and Medical Research (Inserm), Paris, France; The French National Institute for Agricultural Research (INRA), Paris, France.
authors.forename: Ascel
authors.initials: A
authors.lastname: Samba-Louaka
authors.affiliation: Institut Pasteur, Unité des interactions Bactéries-Cellules, Paris, France; The French National Institute of Health and Medical Research (Inserm), Paris, France; The French National Institute for Agricultural Research (INRA), Paris, France.
authors.forename: Jorge M
authors.initials: JM
authors.lastname: Pereira
authors.affiliation: Institut Pasteur, Unité des interactions Bactéries-Cellules, Paris, France; The French National Institute of Health and Medical Research (Inserm), Paris, France; The French National Institute for Agricultural Research (INRA), Paris, France.
authors.forename: Marie-Anne
authors.initials: MA
authors.lastname: Nahori
authors.affiliation: Institut Pasteur, Unité des interactions Bactéries-Cellules, Paris, France; The French National Institute of Health and Medical Research (Inserm), Paris, France; The French National Institute for Agricultural Research (INRA), Paris, France.
authors.forename: Veronique
authors.initials: V
authors.lastname: Villiers
authors.affiliation: Institut Pasteur, Laboratoire développement Lymphocytaire et Oncogénèse, Paris, France; Centre National de la Recherche Scientifique (CNRS) Paris, France.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Deriano
authors.affiliation: Institut Pasteur, Unité des interactions Bactéries-Cellules, Paris, France; The French National Institute of Health and Medical Research (Inserm), Paris, France; The French National Institute for Agricultural Research (INRA), Paris, France.
authors.forename: Mélanie A
authors.initials: MA
authors.lastname: Hamon
authors.affiliation: Institut Pasteur, Unité des interactions Bactéries-Cellules, Paris, France; The French National Institute of Health and Medical Research (Inserm), Paris, France; The French National Institute for Agricultural Research (INRA), Paris, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Cossart
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000494:pharmacology; D004249:DNA Damage; D004261:DNA Replication / Q000235:genetics*; D006360:Heat-Shock Proteins / Q000494:pharmacology; D006460:Hemolysin Proteins / Q000494:pharmacology; D006801:Humans; D008089:Listeria monocytogenes / Q000235:genetics*; D008088:Listeriosis / Q000235:genetics*; D051379:Mice; D015398:Signal Transduction / Q000235:genetics
chemical_list: D001427:Bacterial Toxins; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; C038705:hlyA protein, Listeria monocytogenes