Relationship between agr dysfunction and reduced vancomycin susceptibility in methicillin-susceptible Staphylococcus aureus causing bacteraemia

J Antimicrob Chemother. 2014 Jan;69(1):51-8. doi: 10.1093/jac/dkt337. Epub 2013 Aug 24.

Abstract

Objectives: Limited data exist regarding the role of agr dysfunction in reducing susceptibility to vancomycin in methicillin-susceptible Staphylococcus aureus (MSSA). This study investigated the clinical and molecular epidemiology of MSSA causing bacteraemia, with emphasis on the reduced susceptibility to vancomycin (RSV) phenotype (MIC ≥ 1.5 mg/L) and its relationship with agr dysfunction.

Methods: All MSSA bloodstream isolates obtained at our hospital during 2010 were analysed. Antimicrobial susceptibility was determined and time-kill experiments were performed for oxacillin. Multilocus sequence type and agr genotype were determined and DNA microarray analysis of virulence factors was performed. agr dysfunction was assessed phenotypically and by RT-PCR quantification of RNAIII.

Results: Of 84 MSSA, 55 (65.5%) exhibited the RSV phenotype, comprising 13 clonal complexes. agr II polymorphism was more prevalent in RSV than non-RSV isolates (41.8% versus 17.2%, P = 0.023) and average levels of RNAIII gene expression were higher in RSV than non-RSV isolates (ΔCt 4.05 ± 3.29 versus 1.5 ± 2.11, P = 0.005), implying greater agr dysfunction in RSV MSSA.

Conclusions: We demonstrated a correlation between RSV phenotype in MSSA and reduced agr expression, particularly in association with the agr II genotype. These results may help to understand the role of agr dysfunction in the increased mortality in MSSA infections.

Keywords: MSSA; RSV; reduced susceptibility to vancomycin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Bacteremia / epidemiology*
  • Bacteremia / microbiology
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Drug Resistance, Bacterial*
  • Female
  • Gene Expression Profiling
  • Genotype
  • Humans
  • Male
  • Microarray Analysis
  • Microbial Sensitivity Tests
  • Middle Aged
  • Multilocus Sequence Typing
  • Polymorphism, Genetic
  • Retrospective Studies
  • Spain / epidemiology
  • Staphylococcal Infections / epidemiology*
  • Staphylococcal Infections / microbiology
  • Staphylococcus aureus / drug effects*
  • Staphylococcus aureus / isolation & purification
  • Survival Analysis
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Vancomycin / pharmacology*
  • Virulence Factors / genetics

Substances

  • Agr protein, Staphylococcus aureus
  • Bacterial Proteins
  • Trans-Activators
  • Virulence Factors
  • Vancomycin