Staphylococcus aureus accessory gene regulator (agr) group II: is there a relationship to the development of intermediate-level glycopeptide resistance?

J Infect Dis. 2003 Mar 15;187(6):929-38. doi: 10.1086/368128. Epub 2003 Mar 6.


We previously determined that all 6 Staphylococcus aureus strains with confirmed intermediate-level resistance to glycopeptides (glycopeptide intermediate S. aureus [GISA]) from the United States that we tested belonged to accessory gene regulator (agr) group II. In the present study, we found that 56% of surveyed bloodstream methicillin-resistant S. aureus isolates (n = 148) at our hospital were agr group II, whereas only 24% of methicillin-susceptible S. aureus isolates (n = 33) were agr group II (P = .001). Population analysis of genetically engineered agr-null and parent wild-type strains of groups I, II, and IV revealed that, when agr function is lost, the agr group II knockout S. aureus was most likely to develop glycopeptide heteroresistance after growth in 1 microg/mL but not 16 microg/mL vancomycin. This strain was unique in showing decreased autolysis after growth in these conditions. This study suggests that some S. aureus strains have an intrinsic survival advantage under a glycopeptide selective pressure, which is possibly related to reduced autolysis after exposure to subinhibitory concentrations of glycopeptide.

Publication types

  • Comparative Study

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / physiology*
  • Drug Resistance, Bacterial / genetics*
  • Gene Deletion
  • Humans
  • Methicillin / pharmacology
  • Signal Transduction
  • Staphylococcus aureus / drug effects*
  • Staphylococcus aureus / genetics*
  • Staphylococcus aureus / isolation & purification
  • Trans-Activators / deficiency
  • Trans-Activators / genetics
  • Trans-Activators / physiology*
  • Vancomycin / pharmacology


  • Agr protein, Staphylococcus aureus
  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Trans-Activators
  • Vancomycin
  • Methicillin