Staphylococcus aureus induces DNA damage in host cell

International audience ; Eukaryotic cells are exposed to environmental and endogenous factors that induce DNA damage, thus affecting genomic integrity. The host cells counteract the consequences of lesions by DNA damage response and checkpoint systems that repair DNA structure or trigger cell death when DNA is irreparably damaged. S. aureus, a highly versatile gram-positive bacterium, can cause a multiplicity of human diseases ranging from mild superficial skin to life-threatening disseminated infections. S. aureus is one of the most prevalent pathogen that cause chronic ruminant mastitis that is very difficult to treat. Epithelial cells are able to sense microbes, creating an early line of defense against pathogens. Chronic S. aureus infection is likely to be associated with the internalization of the pathogen by host cells, where bacteria are protected from host defenses. Host cell cycle alteration is one of the highly sophisticated mechanisms pathogens use to hijack the main (defense) functions of the host cells, thus promoting their invasion and colonization. Recently we have shown S. aureus-induced cell cycle alteration in human and bovine epithelial cells.We aimed to investigate whether S. aureus can compromise host genomic integrity.We found that S. aureus can compromise host genomic integrity as indicated by bacteria-induced histone H2AX phosphorylation, a marker of DNA double strand breaks, in human epithelial 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. We demonstrated that this DNA damage is mediated by ROS (reactive oxygen species). 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, showed that ...