The SaeR/S gene regulatory system is essential for innate immune evasion by Staphylococcus aureus

J Infect Dis. 2009 Jun 1;199(11):1698-706. doi: 10.1086/598967.


Methicillin-resistant Staphylococcus aureus is problematic both in hospitals and in the community. Currently, we have limited understanding of mechanisms of innate immune evasion used by S. aureus. To that end, we created an isogenic deletion mutant in strain MW2 (USA400) of the saeR/S 2-component gene regulatory system and studied its role in mouse models of pathogenesis and during human neutrophil interaction. In this study, we demonstrate that saeR/S plays a distinct role in S. aureus pathogenesis and is vital for virulence of MW2 in a mouse model of sepsis. Moreover, deletion of saeR/S significantly impaired survival of MW2 in human blood and after neutrophil phagocytosis. Microarray analysis revealed that SaeR/S of MW2 influences expression of a wide variety of genes with diverse biological functions. These data provide new insight into how virulence is regulated in S. aureus and associates a specific staphylococcal gene-regulatory system with invasive staphylococcal disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Bacterial Proteins / genetics*
  • Disease Models, Animal
  • Immunity, Innate / genetics*
  • Mice
  • Mutagenesis
  • Neutrophils / microbiology
  • Neutrophils / physiology
  • Phagocytosis
  • Polymerase Chain Reaction
  • Protein Kinases / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sepsis / microbiology
  • Sequence Deletion
  • Staphylococcal Infections / immunology*
  • Staphylococcus aureus / genetics*
  • Staphylococcus aureus / immunology*
  • Staphylococcus aureus / isolation & purification
  • Staphylococcus aureus / pathogenicity
  • Transcription Factors
  • Virulence


  • Bacterial Proteins
  • SaeR protein, Staphylococcus aureus
  • Transcription Factors
  • Protein Kinases
  • SaeS protein, Staphylococcus aureus