Inhibition of Virulence Factor Expression in Staphylococcus Aureus by the Staphylococcus Epidermidis Agr Pheromone and Derivatives

FEBS Lett. 1999 May 7;450(3):257-62. doi: 10.1016/s0014-5793(99)00514-1.

Abstract

The agr quorum-sensing system in Staphylococci controls the production of surface proteins and exoproteins. In the pathogenic species Staphylococcus aureus, these proteins include many virulence factors. The extracellular signal of the quorum-sensing system is a thiolactone-containing peptide pheromone, whose sequence varies among the different staphylococcal strains. We demonstrate that a synthetic Staphylococcus epidermidis pheromone is a competent inhibitor of the Staphylococcus aureus agr system. Derivatives of the pheromone, in which the N-terminus or the cyclic bond structure was changed, were synthesized and their biological activity was determined. The presence of a correct N-terminus and a thiolactone were absolute prerequisites for an agr-activating effect in S. epidermidis, whereas inhibition of the S. aureus agr system was less dependent on the original structure. Our results show that effective quorum-sensing blockers that suppress the expression of virulence factors in S. aureus can be designed based on the S. epidermidis pheromone.

MeSH terms

  • Bacterial Proteins / antagonists & inhibitors
  • Bacterial Proteins / biosynthesis*
  • Bacterial Proteins / chemistry
  • Molecular Structure
  • Oligopeptides
  • Phenotype
  • Pheromones / antagonists & inhibitors
  • Pheromones / biosynthesis*
  • Pheromones / chemistry
  • Staphylococcus aureus / metabolism*
  • Staphylococcus aureus / pathogenicity
  • Staphylococcus epidermidis / metabolism*
  • Trans-Activators*
  • Transcription Factors / antagonists & inhibitors
  • Transcription Factors / biosynthesis*
  • Transcription Factors / chemistry
  • Virulence

Substances

  • Agr protein, Staphylococcus aureus
  • Bacterial Proteins
  • Oligopeptides
  • Pheromones
  • Trans-Activators
  • Transcription Factors