title: Relationship between agr dysfunction and reduced vancomycin susceptibility in methicillin-susceptible Staphylococcus aureus causing bacteraemia.
abstract: OBJECTIVE
  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.
authors: Microbiology Department, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain.
authors: Esther
authors: E
authors: Viedma
authors: Francisca
authors: F
authors: Sanz
authors: M Angeles
authors: MA
authors: Orellana
authors: Rafael
authors: R
authors: San Juan
authors: Jose Maria
authors: JM
authors: Aguado
authors: Joaquín R
authors: JR
authors: Otero
authors: Fernando
authors: F
authors: Chaves
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016470:Bacteremia / Q000453:epidemiology* / Q000382:microbiology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D024881:Drug Resistance, Bacterial; D005260:Female; D020869:Gene Expression Profiling; D005838:Genotype; D006801:Humans; D008297:Male; D046228:Microarray Analysis; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D058885:Multilocus Sequence Typing; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D013030:Spain / Q000453:epidemiology; D013203:Staphylococcal Infections / Q000453:epidemiology* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000302:isolation & purification; D016019:Survival Analysis; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014640:Vancomycin / Q000494:pharmacology*; D037521:Virulence Factors / Q000235:genetics
chemical_list: C095698:Agr protein, Staphylococcus aureus; D001426:Bacterial Proteins; D015534:Trans-Activators; D037521:Virulence Factors; D014640:Vancomycin
keywords: MSSA; RSV; reduced susceptibility to vancomycin