title: High in vitro antimicrobial activity of synthetic antimicrobial peptidomimetics against staphylococcal biofilms.
abstract: OBJECTIVE
  The aim of the study was to investigate the antimicrobial effect of different antibiotics and synthetic antimicrobial peptidomimetics (SAMPs) on staphylococcal biofilms.
  
  
  METHODS
  Biofilms of six staphylococcal strains (two Staphylococcus haemolyticus, two Staphylococcus epidermidis and two Staphylococcus aureus isolates) were grown for 24 h in microtitre plates. They were washed and treated for 24 h with different concentrations of linezolid, tetracycline, rifampicin and vancomycin and four different SAMPs. After treatment, the redox indicator Alamar Blue was used to quantify metabolic activity of bacteria in biofilms, and confocal laser scanning microscopy with LIVE/DEAD staining was used to further elucidate any effects.
  
  
  RESULTS
  At MIC levels, rifampicin and tetracycline showed a marked reduction of metabolic activity in the S. epidermidis and S. haemolyticus biofilm. Linezolid had a moderate effect and vancomycin had a poor effect. MIC x10 and MIC x100 improved the antimicrobial activity of all antibiotics, especially vancomycin. However, metabolic activity was not completely suppressed in strong biofilm-producing strains. At MIC x10, the three most effective SAMPs (Ltx5, Ltx9 and Ltx10) were able to completely eliminate metabolic activity in the S. epidermidis and S. haemolyticus biofilms, which was also confirmed by complete cell death using confocal laser scanning microscopy investigations. Although none of the Ltx SAMPs could fully suppress metabolic activity in the S. aureus biofilm, their effect was superior to all tested antibiotics.
  
  
  CONCLUSIONS
  SAMPs had superior antimicrobial activity in staphylococcal biofilms compared with conventional antibiotics and are potential new therapeutic agents for biofilm-associated infections.
authors.affiliation: Department of Paediatrics, University Hospital of North-Norway, Tromsø, Norway.
authors.forename: Kristina
authors.initials: K
authors.lastname: Flemming
authors.forename: Claus
authors.initials: C
authors.lastname: Klingenberg
authors.forename: Jorun Pauline
authors.initials: JP
authors.lastname: Cavanagh
authors.forename: Merethe
authors.initials: M
authors.lastname: Sletteng
authors.forename: Wenche
authors.initials: W
authors.lastname: Stensen
authors.forename: John Sigurd
authors.initials: JS
authors.lastname: Svendsen
authors.forename: Trond
authors.initials: T
authors.lastname: Flaegstad
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability; D018613:Microscopy, Confocal; D010078:Oxazines / Q000378:metabolism; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000502:physiology; D013212:Staphylococcus epidermidis / Q000187:drug effects* / Q000502:physiology; D041162:Staphylococcus haemolyticus / Q000187:drug effects* / Q000502:physiology; D014966:Xanthenes / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D010078:Oxazines; D014966:Xanthenes; C005843:resazurin