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Staphylococcus aureus induces DNA damage in host cell

Abstract : Staphylococcus aureus causes serious medical problems in human and animals. Here we show thatS. aureus can compromise host genomic integrity as indicated by bacteria-induced histone H2AXphosphorylation, a marker of DNA double strand breaks (DSBs), in human cervix cancer HeLa andosteoblast-like MG-63 cells. This DNA damage is mediated by alpha phenol-soluble modulins (PSMα1–4),while a specific class of lipoproteins (Lpls), encoded on a pathogenicity island in S. aureus, dampens theH2AX phosphorylation thus counteracting the DNA damage. This DNA damage is mediated by reactiveoxygen species (ROS), which promotes oxidation of guanine forming 7,8-dihydro-8-oxoguanine (8-oxoG). DNA damage is followed by the induction of DNA repair that involves the ATM kinase-signalingpathway. An examination of S. aureus strains, isolated from the same patient during acute initial andrecurrent bone and joint infections (BJI), showed that recurrent strains produce lower amounts of Lpls,induce stronger DNA-damage and prompt the G2/M transition delay to a greater extent that suggest aninvolvement of these mechanisms in adaptive processes of bacteria during chronicization. Our findingsredefine our understanding of mechanisms of S. aureus-host interaction and suggest that the balancebetween the levels of PSMα and Lpls expression impacts the persistence of the infection.
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Déposant : Laurent Jonchère <>
Soumis le : mercredi 12 juin 2019 - 20:43:01
Dernière modification le : vendredi 19 février 2021 - 14:51:18

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Martine Deplanche, Nassim Mouhali, Minh-Thu Nguyen, Chantal Cauty, Frederic Ezan, et al.. Staphylococcus aureus induces DNA damage in host cell. Scientific Reports, Nature Publishing Group, 2019, 9 (1), pp.7694. ⟨10.1038/s41598-019-44213-3⟩. ⟨hal-02153435⟩

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