Staphylococcus aureus nuclease is an SaeRS-dependent virulence factor

Area of Science:

• Microbiology
• Bacterial Pathogenesis
• Molecular Biology

Background:

• Bacterial pathogens like Staphylococcus aureus secrete nuclease (Nuc) enzymes to counteract host immune responses.
• Previous research suggested Nuc regulation by the agr quorum-sensing system, but recent data pointed to the SaeRS two-component system.

Purpose of the Study:

• To investigate the regulatory mechanism controlling Staphylococcus aureus nuclease (Nuc) gene expression.
• To determine the role of the SaeRS two-component system and the agr system in Nuc regulation.
• To evaluate the contribution of Nuc to virulence in vivo.

Main Methods:

• Reporter gene fusions, immunoblotting, Nuc activity assays, promoter mapping, and DNA-binding studies were employed.
• SaeRS-dependent Nuc regulation was assessed across diverse S. aureus isolates.
• A mouse model of peritonitis was used to study in vivo Nuc expression and virulence in community-associated methicillin-resistant S. aureus (CA MRSA).

Main Results:

• The nuc gene is directly controlled by the SaeRS two-component system, with no significant link to the agr system identified.
• SaeRS-dependent Nuc regulation was conserved among various S. aureus isolates.
• In vivo, Nuc activity was expressed in an SaeRS-dependent manner in a CA MRSA peritonitis model, and Nuc was crucial for survival.

Conclusions:

• The SaeRS two-component system is the primary regulator of the nuclease (Nuc) gene in Staphylococcus aureus.
• Nuclease is a significant virulence factor contributing to invasive disease and in vivo survival.
• Natural polymorphisms in SaeRS proteins can influence Nuc regulation in specific strains.