title: Panton-Valentine leucocidin expression by Staphylococcus aureus exposed to common antibiotics.
abstract: OBJECTIVE
  We set out to investigate the impact of common antibiotics on Panton-Valentine Leucocidin (PVL) expression by methicillin-sensitive Staphylococcus aureus (MSSA). PVL expression by methicillin-resistant S. aureus (MRSA) is reportedly enhanced by β-lactams, but inhibited by protein-synthesis inhibitors, a fact that has influenced management of infections associated with PVL. Although PVL is more frequently associated with MSSA than MRSA in the UK, the effect of antibiotics on PVL expression by MSSA has not been fully addressed.
  
  
  METHODS
  MSSA was cultured in vitro with varying concentrations of flucloxacillin, clindamycin or linezolid and PVL expression measured by qRT-PCR and Western blotting. A murine MSSA abscess model was developed to measure leucocidin expression in vivo following antibiotic treatment.
  
  
  RESULTS
  9% (27/314) of MSSA isolates from patients with uncomplicated community skin/soft tissue infections were positive for PVL genes (lukFS-PV). PVL expression by MSSA in broth was unaffected by varying concentrations of flucloxacillin, clindamycin or linezolid. In a murine abscess model, treatment with flucloxacillin did, however, enhance in vivo MSSA lukF-PV transcription and this was sustained even when flucloxacillin was combined with clindamycin, or clindamycin plus linezolid. Notwithstanding increased leucocidin transcription, functional leucotoxin activity was not enhanced. Treatment with flucloxacillin plus clindamycin significantly decreased leucotoxin activity, but the addition of a second protein synthesis inhibitor, linezolid, did not confer benefit.
  
  
  CONCLUSIONS
  Our results suggest flucloxacillin in combination with a single protein-synthesis inhibitor such as clindamycin would give the best treatment outcome.
authors.affiliation: Infectious Diseases & Immunity, Imperial College London, London, United Kingdom.
authors.forename: Claire E
authors.initials: CE
authors.lastname: Turner
authors.affiliation: Infectious Diseases & Immunity, Imperial College London, London, United Kingdom. Electronic address: s.sriskandan@imperial.ac.uk.
authors.forename: Shiranee
authors.initials: S
authors.lastname: Sriskandan
mesh_terms: D000038:Abscess / Q000382:microbiology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001427:Bacterial Toxins / Q000235:genetics*; D015153:Blotting, Western; D002981:Clindamycin / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D005098:Exotoxins / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D006801:Humans; D007956:Leukocidins / Q000235:genetics*; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D060888:Real-Time Polymerase Chain Reaction; D018461:Soft Tissue Infections / Q000382:microbiology; D013203:Staphylococcal Infections / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity
chemical_list: D000900:Anti-Bacterial Agents; D001427:Bacterial Toxins; D005098:Exotoxins; D007956:Leukocidins; C078284:Panton-Valentine leukocidin; C018579:leukotoxin; D002981:Clindamycin
keywords: Abscess model; Clindamycin; Flucloxacillin; Leucocidins; Linzeolid; Methicillin sensitive Staphylococcus aureus; Panton–Valentine leucocidin; Protein synthesis inhibitors; β-lactams