Staphylococcal DNA Repair Is Required for Infection

Area of Science:

• Microbiology
• Immunology
• Molecular Biology

Background:

• Bacteria must survive host immune defenses to cause infection.
• Neutrophils pose a significant threat to bacteria via reactive oxygen species (ROS).
• Mechanisms of bacterial DNA damage and repair during infection are not fully understood.

Purpose of the Study:

• Identify mechanisms of Staphylococcus aureus survival against host immune attack.
• Investigate the role of DNA repair in bacterial pathogenesis.
• Determine how bacterial DNA is damaged by neutrophils.

Main Methods:

• Transposon mutagenesis to identify survival genes.
• Murine models of infection (systemic and skin).
• Fluorescent reporter system to detect DNA double-strand breaks.
• Analysis of RexAB homologs in other Gram-positive bacteria.

Main Results:

• The rexBA operon is essential for S. aureus survival in human blood and virulence in mice.
• RexAB repairs DNA double-strand breaks initiated by neutrophil ROS.
• ROS-induced DNA damage triggers the SOS response in S. aureus.
• RexAB homologs are important for Enterococcus faecalis and Streptococcus gordonii survival in blood.

Conclusions:

• Bacterial DNA is a target of immune cell-mediated damage.
• The RexAB enzyme, an AddAB-family complex, repairs ROS-induced DNA double-strand breaks.
• DNA repair is critical for Gram-positive pathogen survival and infection progression.