title: Staphylococcus aureus accessory gene regulator (agr) group II: is there a relationship to the development of intermediate-level glycopeptide resistance?
abstract: 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.
authors.affiliation: Department of Medicine, Division of Laboratory and Transfusion Medicine and Harvard Medical School, Boston, Massachussetts, USA. gsakoulas@crystalrunhealthcare.com
authors.forename: George
authors.initials: G
authors.lastname: Sakoulas
authors.forename: George M
authors.initials: GM
authors.lastname: Eliopoulos
authors.forename: Robert C
authors.initials: RC
authors.lastname: Moellering
authors.forename: Richard P
authors.initials: RP
authors.lastname: Novick
authors.forename: Lata
authors.initials: L
authors.lastname: Venkataraman
authors.forename: Christine
authors.initials: C
authors.lastname: Wennersten
authors.forename: Paola C
authors.initials: PC
authors.lastname: DeGirolami
authors.forename: Mitchell J
authors.initials: MJ
authors.lastname: Schwaber
authors.forename: Howard S
authors.initials: HS
authors.lastname: Gold
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D017353:Gene Deletion; D006801:Humans; D008712:Methicillin / Q000494:pharmacology; D015398:Signal Transduction; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D014640:Vancomycin / Q000494:pharmacology
chemical_list: C095698:Agr protein, Staphylococcus aureus; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D015534:Trans-Activators; D014640:Vancomycin; D008712:Methicillin