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.