The role of innate immunity in promoting SaeR/S-mediated virulence in Staphylococcus aureus

J Innate Immun. 2014;6(1):21-30. doi: 10.1159/000351200. Epub 2013 Jun 29.


The ability of Staphylococcus aureus to infect tissues is dependent on precise control of virulence through gene-regulatory systems. While the SaeR/S two-component system has been shown to be a major regulator of S. aureus virulence, the influence of the host environment on SaeR/S-regulated genes (saeR/S targets) remains incompletely defined. Using QuantiGene 2.0 transcriptional assays, we examined expression of genes with the SaeR binding site in USA300 exposed to human and mouse neutrophils and host-derived peptides and during subcutaneous skin infection. We found that only some of the saeR/S targets, as opposed to the entire SaeR/S virulon, were activated within 5 and 10 min of interacting with human neutrophils as well as α-defensin. Furthermore, mouse neutrophils promoted transcription of saeR/S targets despite lacking α-defensin, and the murine skin environment elicited a distinctive expression profile of saeR/S targets. These findings indicate that saeR/S-mediated transcription is unique to and dependent on specific host stimuli. By using isogenic USA300ΔsaeR/S and USA300Δagr knockout strains, we also determined that SaeR/S is the major regulator of virulence factors, while Agr, a quorum-sensing two-component system, has moderate influence on transcription of the saeR/S targets under the tested physiological conditions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins / metabolism*
  • Gene Expression Regulation, Bacterial
  • Gene Knockout Techniques
  • Host Specificity
  • Host-Pathogen Interactions
  • Humans
  • Immunity, Innate
  • Mice
  • Microarray Analysis
  • Neutrophils / immunology*
  • Neutrophils / microbiology
  • Skin / immunology*
  • Skin / microbiology
  • Staphylococcal Infections / immunology*
  • Staphylococcus aureus / immunology*
  • Staphylococcus aureus / pathogenicity
  • Trans-Activators
  • Transcription Factors
  • Transcriptome
  • Virulence / genetics
  • alpha-Defensins / metabolism


  • Agr protein, Staphylococcus aureus
  • Bacterial Proteins
  • SaeR protein, Staphylococcus aureus
  • Trans-Activators
  • Transcription Factors
  • alpha-Defensins