Staphylococcus aureus induces DNA damage in host cell

Area of Science:

• Microbiology
• Genomics
• Cell Biology

Background:

• Staphylococcus aureus is a significant pathogen causing severe human and animal infections.
• Understanding host-pathogen interactions is crucial for developing effective treatments against S. aureus.

Purpose of the Study:

• To investigate the mechanisms by which S. aureus compromises host genomic integrity.
• To identify bacterial factors involved in DNA damage and repair.
• To explore the role of these mechanisms in S. aureus infection chronicity.

Main Methods:

• Utilized human cervix cancer HeLa and osteoblast-like MG-63 cells to assess DNA damage.
• Measured histone H2AX phosphorylation as a marker for DNA double strand breaks (DSBs).
• Investigated the roles of phenol-soluble modulins (PSMα) and lipoproteins (Lpls) in DNA damage induction and counteraction.
• Analyzed S. aureus strains from acute and recurrent bone and joint infections (BJI).

Main Results:

• S. aureus induces DNA double strand breaks (DSBs) in host cells, evidenced by histone H2AX phosphorylation.
• Alpha phenol-soluble modulins (PSMα) mediate this DNA damage, while lipoproteins (Lpls) counteract it.
• DNA damage is linked to reactive oxygen species (ROS) and guanine oxidation (8-oxoG), activating the ATM kinase-signaling pathway for DNA repair.
• Recurrent S. aureus strains exhibit lower Lpl production, induce greater DNA damage, and cause more significant G2/M cell cycle delay compared to acute strains.

Conclusions:

• The balance between PSMα and Lpl expression in S. aureus influences host genomic integrity.
• These mechanisms, particularly the altered expression in recurrent strains, may contribute to bacterial adaptation and persistence during chronic infections.
• Findings offer new insights into S. aureus-host interactions and potential therapeutic targets.