Richter Katharina, Ramezanpour Mahnaz, Thomas Nicky, Prestidge Clive A, Wormald Peter-John, Vreugde Sarah
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.
Int Forum Allergy Rhinol. 2016 Jul;6(7):737-43. doi: 10.1002/alr.21735. Epub 2016 Feb 25.
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.
生物膜是嵌入保护性基质中的细菌簇，常常导致治疗失败并增加反复感染的风险。特别是，金黄色葡萄球菌生物膜与一系列对抗生素越来越耐药的慢性和医院感染有关。本研究提出了一种针对细菌生长、存活和发病机制所必需的铁代谢的新型干预策略，使用去铁酮（Def）和镓原卟啉（GaPP）化合物。
用Def/GaPP作为单一和联合处理对金黄色葡萄球菌生物膜进行挑战。通过AlamarBlue活力测定法和共聚焦显微镜评估体外抗生物膜功效。通过对小鼠成纤维细胞（L929）和人支气管上皮细胞（Nuli-1）进行乳酸脱氢酶测定来检测处理的体外细胞毒性。
Def（20 mM）和GaPP（200 μg/mL）单一疗法处理2小时分别显示出35%和74%的生物膜清除率，而同时给予Def/GaPP显示出55%的生物膜清除率。相比之下，连续处理（2小时Def后接2小时GaPP）实现了95%的生物膜清除率。细胞毒性研究表明所有处理均无细胞危害。
本研究证明了一种针对金黄色葡萄球菌生物膜、靶向细菌铁代谢的新型治疗组合的体外疗效。连续的Def/GaPP处理显示出比单个化合物显著增强的生物膜疗效，同时对两种细胞系无毒。这种新型治疗组合是对抗与金黄色葡萄球菌相关的生物膜感染的一种有前景的方法，具有很高的未来临床应用潜力。
