期刊
INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY
卷 6, 期 7, 页码 737-743出版社
WILEY
DOI: 10.1002/alr.21735
关键词
biofilms; deferiprone; gallium-protoporphyrin IX; iron metabolism; S; aureus
资金
- Hospital Research Foundation, Woodville, Australia
- Department of Surgery, Otolaryngology Head and Neck Surgery, University of Adelaide, Adelaide, Australia
- National Health and Medical Research Council (NHMRC), Australia [GNT1090898]
- Florey Medical Research Foundation, Faculty of Health Sciences, University of Adelaide, Adelaide, Australia
BackgroundBiofilms 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). MethodsS. 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). ResultsDef (20 mM) and GaPP (200 g/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. ConclusionThis 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. (C) 2016 ARS-AAOA, LLC.
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