RNAIII-independent target gene control by the agr quorum-sensing system: insight into the evolution of virulence regulation in Staphylococcus aureus

Mol Cell. 2008 Oct 10;32(1):150-8. doi: 10.1016/j.molcel.2008.08.005.


Cell-density-dependent gene regulation by quorum-sensing systems has a crucial function in bacterial physiology and pathogenesis. We demonstrate here that the Staphylococcus aureus agr quorum-sensing regulon is divided into (1) control of metabolism and PSM cytolysin genes, which occurs independently of the small regulatory RNA RNAIII, and (2) RNAIII-dependent control of additional virulence genes. Remarkably, PSM expression was regulated by direct binding of the AgrA response regulator. Our findings suggest that quorum-sensing regulation of PSMs was established before wide-ranging control of virulence was added to the agr regulon, which likely occurred by development of the RNAIII-encoding region around the gene encoding the PSM delta-toxin. Moreover, the agr regulon in the community-associated methicillin-resistant S. aureus MW2 considerably differed from that previously determined using laboratory strains. By establishing a two-level model of quorum-sensing target gene regulation in S. aureus, our study gives important insight into the evolution of virulence control in this leading human pathogen.

Publication types

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

MeSH terms

  • Bacterial Proteins / genetics
  • Bacterial Proteins / physiology*
  • Bacterial Toxins / genetics
  • Base Sequence
  • DNA, Bacterial / genetics
  • Evolution, Molecular
  • Gene Expression Regulation, Bacterial
  • Genes, Bacterial*
  • Humans
  • Methicillin Resistance / genetics
  • Models, Biological
  • Molecular Sequence Data
  • Promoter Regions, Genetic
  • Quorum Sensing / genetics
  • Quorum Sensing / physiology
  • RNA, Bacterial / genetics*
  • Staphylococcus aureus / drug effects
  • Staphylococcus aureus / genetics*
  • Staphylococcus aureus / pathogenicity
  • Staphylococcus aureus / physiology*
  • Trans-Activators / genetics
  • Trans-Activators / physiology*
  • Virulence / genetics
  • Virulence / physiology


  • Agr protein, Staphylococcus aureus
  • Bacterial Proteins
  • Bacterial Toxins
  • DNA, Bacterial
  • RNA, Bacterial
  • RNAIII, Staphylococcus aureus
  • Trans-Activators