Staphylococcus aureusAccessory 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.

Characterisation of virulence genes in methicillin susceptible and resistant Staphylococcus aureus isolates from a paediatric population in a university hospital of Medellín, Colombia

“…It has been suggested that the acquisition of antibiotic resistance in S. aureus involves changes in virulence factor secretion due to the fitness cost associated with the expression of resistance (Sakoulas et al 2003, Gill et al 2005 and it is reflected in decreased toxin expression (Collins et al 2010, Otto 2010. Therefore, it is not surprising that the results of the present study confirmed this by showing that virulence factor gene carriage was more diverse and abundant in MSSA than in MRSA strains.…”

Reduced Vancomycin Susceptibility inStaphylococcus aureus, Including Vancomycin-Intermediate and Heterogeneous Vancomycin-Intermediate Strains: Resistance Mechanisms, Laboratory Detection, and Clinical Implications

“…A number of studies have linked alterations in agr activation or function with vancomycin tolerance, an increased tendency to develop vancomycin resistance, and the presence of the hVISA or VISA phenotype (121,269,295,296,357). In a number of these studies, determinations of agr activity were performed by the analysis of delta-hemolysin production on sheep blood agar; however, this is only a semiquantitative measure (296).…”

“…Initially, it appeared that agr group II isolates were overrepresented in VISA strains from around the world (369); however, a subsequent study from Europe demonstrated that many of their VISA and hVISA isolates were of agr group I (295,296). In addition, it was demonstrated that S. aureus from agr groups I to IV all develop intermediate vancomycin resistance upon in vitro exposure to the drug (358).…”

“…In a number of in vitro studies, reduced agr function has been shown to favor the development of vancomycin resistance (295,296,358); however, an association between agr function and teicoplanin resistance development was not demonstrated (281). Assuming that the relationship between agr function and the development of vancomycin resistance exists, it is worth noting that in one study, 48% of hospital MRSA strains were found to have reduced agr function, compared to 3.5% of community-associated MRSA strains (357), suggesting a possible higher tendency for hospital MRSA strains to develop into hVISA or VISA strains.…”

“…A clinical study also linked agr group II polymorphisms with poor responses to vancomycin therapy for patients with MRSA infections (211). In addition, a loss of agr function was associated with a reduced susceptibility to platelet microbiocidal protein and reduced autolysis, a common feature of hVISA and VISA strains (295,296).…”