Staphylococcus aureus induces DNA damage in host cell

Sci Rep. 2019 May 22;9(1):7694. doi: 10.1038/s41598-019-44213-3.


Staphylococcus aureus causes serious medical problems in human and animals. Here we show that S. aureus can compromise host genomic integrity as indicated by bacteria-induced histone H2AX phosphorylation, a marker of DNA double strand breaks (DSBs), in human cervix cancer HeLa and osteoblast-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 the H2AX phosphorylation thus counteracting the DNA damage. This DNA damage is mediated by reactive oxygen 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-signaling pathway. An examination of S. aureus strains, isolated from the same patient during acute initial and recurrent 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 an involvement of these mechanisms in adaptive processes of bacteria during chronicization. Our findings redefine our understanding of mechanisms of S. aureus-host interaction and suggest that the balance between the levels of PSMα and Lpls expression impacts the persistence of the infection.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / pharmacology
  • Arthritis, Infectious / microbiology
  • Bacterial Toxins / pharmacology
  • Cell Line, Tumor
  • DNA Damage*
  • DNA Repair
  • Etoposide / pharmacology
  • G2 Phase Cell Cycle Checkpoints
  • Genomic Islands
  • Guanine / analogs & derivatives
  • Guanine / metabolism
  • HeLa Cells / microbiology
  • Histones / analysis
  • Host-Pathogen Interactions
  • Humans
  • Lipoproteins / pharmacology
  • Osteitis / microbiology
  • Osteoblasts / microbiology
  • Oxidative Stress
  • Phosphorylation
  • Protein Processing, Post-Translational
  • Reactive Oxygen Species
  • Staphylococcal Infections / microbiology
  • Staphylococcus aureus / pathogenicity*


  • Bacterial Toxins
  • H2AX protein, human
  • Histones
  • Lipoproteins
  • Reactive Oxygen Species
  • staphylococcal delta toxin
  • 8-hydroxyguanine
  • Guanine
  • Etoposide
  • Acetylcysteine