title: Listeria monocytogenes induces host DNA damage and delays the host cell cycle to promote infection.
abstract: Listeria monocytogenes (Lm) is a human intracellular pathogen widely used to uncover the mechanisms evolved by pathogens to establish infection. However, its capacity to perturb the host cell cycle was never reported. We show that Lm infection affects the host cell cycle progression, increasing its overall duration but allowing consecutive rounds of division. A complete Lm infectious cycle induces a S-phase delay accompanied by a slower rate of DNA synthesis and increased levels of host DNA strand breaks. Additionally, DNA damage/replication checkpoint responses are triggered in an Lm dose-dependent manner through the phosphorylation of DNA-PK, H2A.X, and CDC25A and independently from ATM/ATR. While host DNA damage induced exogenously favors Lm dissemination, the override of checkpoint pathways limits infection. We propose that host DNA replication disturbed by Lm infection culminates in DNA strand breaks, triggering DNA damage/replication responses, and ensuring a cell cycle delay that favors Lm propagation.
authors.affiliation: Group of Molecular Microbiology, Infection and Immunity; IBMC - Instituto de Biologia Molecular e Celular; Universidade do Porto; Porto, Portugal.
authors.forename: Elsa
authors.initials: E
authors.lastname: Leitão
authors.affiliation: Group of Molecular Microbiology, Infection and Immunity; IBMC - Instituto de Biologia Molecular e Celular; Universidade do Porto; Porto, Portugal.
authors.forename: Ana Catarina
authors.initials: AC
authors.lastname: Costa
authors.affiliation: Group of Molecular Microbiology, Infection and Immunity; IBMC - Instituto de Biologia Molecular e Celular; Universidade do Porto; Porto, Portugal.
authors.forename: Cláudia
authors.initials: C
authors.lastname: Brito
authors.affiliation: Group of Molecular Microbiology, Infection and Immunity; IBMC - Instituto de Biologia Molecular e Celular; Universidade do Porto; Porto, Portugal.
authors.forename: Lionel
authors.initials: L
authors.lastname: Costa
authors.affiliation: Group of Molecular Microbiology, Infection and Immunity; IBMC - Instituto de Biologia Molecular e Celular; Universidade do Porto; Porto, Portugal.
authors.forename: Rita
authors.initials: R
authors.lastname: Pombinho
authors.affiliation: Group of Molecular Microbiology, Infection and Immunity; IBMC - Instituto de Biologia Molecular e Celular; Universidade do Porto; Porto, Portugal.
authors.forename: Didier
authors.initials: D
authors.lastname: Cabanes
authors.affiliation: Group of Molecular Microbiology, Infection and Immunity; IBMC - Instituto de Biologia Molecular e Celular; Universidade do Porto; Porto, Portugal.
authors.forename: Sandra
authors.initials: S
authors.lastname: Sousa
mesh_terms: D002135:Calcium-Binding Proteins / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology*; D045744:Cell Line, Tumor; D053960:DNA Breaks; D004249:DNA Damage; D004260:DNA Repair; D004261:DNA Replication; D054884:Host-Pathogen Interactions; D006801:Humans; D008089:Listeria monocytogenes / Q000502:physiology*; D008088:Listeriosis / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D016196:S Phase; D020687:cdc25 Phosphatases / Q000378:metabolism
chemical_list: C109198:CIB1 protein, human; D002135:Calcium-Binding Proteins; C517004:CDC25A protein, human; D020687:cdc25 Phosphatases
keywords: CDC25A; DNA damage; DNA-PK; Listeria monocytogenes; bacterial infection; host cell cycle