Membrane damage elicits an immunomodulatory program in Staphylococcus aureus.

Area of Science:

• Microbiology
• Bacterial Pathogenesis
• Host-Pathogen Interactions

Background:

• Staphylococcus aureus utilizes the HrtAB system, a hemin-regulated ABC transporter, for protection against hemin toxicity.
• Strains lacking the HrtAB system exhibit hyper-virulence and interfere with neutrophil recruitment.
• Heme accumulation was previously hypothesized to trigger S. aureus's anti-neutrophil response.

Purpose of the Study:

• To investigate the role of HrtA's ATPase activity versus its physical absence in S. aureus's immunomodulatory response.
• To elucidate the mechanism by which S. aureus senses and responds to hemin exposure and potential membrane damage.

Main Methods:

• Comparison of secreted protein profiles in S. aureus strains with wild-type HrtA, catalytically inactive HrtA, and absent HrtA.
• Assessment of membrane integrity in S. aureus strains lacking HrtA.
• Treatment of wild-type S. aureus with anti-staphylococcal channel-forming peptides to mimic membrane damage.

Main Results:

• S. aureus strains expressing catalytically inactive HrtA did not show the same secreted protein profile as strains lacking HrtA, indicating HrtA's physical absence is key.
• HrtB over-expression in the absence of HrtA compromised membrane integrity, suggesting pore formation.
• Treatment with channel-forming peptides induced a secreted protein profile similar to DeltahrtA strains exposed to hemin.

Conclusions:

• The physical absence of HrtA, rather than its ATPase activity, is responsible for the increased expression of immunomodulatory factors.
• Hemin-mediated HrtB over-expression in the absence of HrtA leads to membrane damage, which S. aureus senses.
• S. aureus activates a gene expression program in response to membrane damage to protect itself from the host's innate immune response.