title: Mind "De GaPP": in vitro efficacy of deferiprone and gallium-protoporphyrin against Staphylococcus aureus biofilms.
abstract: Biofilms are clusters of bacteria embedded in a protective matrix that frequently cause failure of medical treatments and increase the risk of recurrent infections. In particular, Staphylococcus aureus biofilms are associated with a series of chronic and nosocomial infections that are increasingly resistant to antibiotics. This study proposes a novel intervention strategy targeting the essential iron metabolism for bacterial growth, survival and pathogenesis using the compounds deferiprone (Def) and gallium-protoporphyrin (GaPP).
  
  
  
  S. aureus biofilms were challenged with Def/GaPP as single and dual treatments. In vitro anti-biofilm efficacy was assessed by the AlamarBlue viability assay and confocal microscopy. In vitro cytotoxicity of the treatments was examined by the lactate dehydrogenase assay on mouse fibroblast (L929) and human bronchial epithelial cells (Nuli-1).
  
  
  
  Def (20 mM) and GaPP (200 μg/mL) monotherapy for 2 hours showed 35% and 74% biofilm removal, respectively, whereas simultaneous Def/GaPP administration showed 55% biofilm removal. In contrast, the consecutive treatment (2 hours Def followed by 2 hours GaPP) achieved 95% biofilm removal. Cytotoxicity studies indicated no cell hazard in all treatments.
  
  
  
  This study demonstrated the in vitro efficacy of a novel treatment combination against S. aureus biofilms targeting the bacterial iron metabolism. The consecutive Def/GaPP treatment showed significantly enhanced biofilm efficacy than the individual compounds, while being not toxic to 2 cell lines. This novel treatment combination is a promising approach to combat S. aureus-associated biofilm infections having high potential for future clinical application.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Adelaide, The Queen Elizabeth Hospital, Basil Hetzel Institute for Translational Health Research, Woodville South, Australia.
authors.forename: Katharina
authors.initials: K
authors.lastname: Richter
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Adelaide, The Queen Elizabeth Hospital, Basil Hetzel Institute for Translational Health Research, Woodville South, Australia.
authors.forename: Mahnaz
authors.initials: M
authors.lastname: Ramezanpour
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Adelaide, The Queen Elizabeth Hospital, Basil Hetzel Institute for Translational Health Research, Woodville South, Australia.|School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia.
authors.forename: Nicky
authors.initials: N
authors.lastname: Thomas
authors.affiliation: School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia.
authors.forename: Clive A
authors.initials: CA
authors.lastname: Prestidge
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Adelaide, The Queen Elizabeth Hospital, Basil Hetzel Institute for Translational Health Research, Woodville South, Australia.
authors.forename: Peter-John
authors.initials: PJ
authors.lastname: Wormald
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Adelaide, The Queen Elizabeth Hospital, Basil Hetzel Institute for Translational Health Research, Woodville South, Australia.
authors.forename: Sarah
authors.initials: S
authors.lastname: Vreugde
mesh_terms: D018441:Biofilms / Q000187:drug effects / Q000254:growth & development; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D000077543:Deferiprone; D005708:Gallium / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D011524:Protoporphyrins / Q000494:pharmacology*; D011728:Pyridones / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development
chemical_list: D011524:Protoporphyrins; D011728:Pyridones; D000077543:Deferiprone; D005708:Gallium
keywords: S. aureus; biofilms; deferiprone; gallium-protoporphyrin IX; iron metabolism