Eradication of Pseudomonas aeruginosa biofilms and persister cells using an electrochemical scaffold and enhanced antibiotic susceptibility.
Eradication of Pseudomonas aeruginosa biofilms and persister cells using an electrochemical scaffold and enhanced antibiotic susceptibility.
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DOI：
10.1038/s41522-016-0003-0
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发表时间：
2016
影响因子：
9.2
通讯作者：
Beyenal H
中科院分区：
文献类型：
--
作者：
Sultana ST;Call DR;Beyenal H
已知慢性伤口中的生物膜含有持续存在的亚群，其表现出增强的多药耐受性，并且在治疗性处理后可以快速反弹。这些“持久细胞”的存在是抗生素治疗失败和生物膜不完全消除的部分原因。电化学方法结合抗生素已被认为是生物膜和持久性细胞消除的有效替代方案，但提高抗生素疗效的作用机制仍不清楚。在这项工作中，电化学支架（e-支架），电化学产生恒定浓度的H2 O2的研究作为一种手段，提高妥布霉素的敏感性在预生长的铜绿假单胞菌PAO 1生物膜和攻击persister细胞。结果显示，e-支架增强了铜绿假单胞菌PAO 1生物膜中的妥布霉素敏感性，其在40 μg/ml妥布霉素时达到最大敏感性，并完全消除（相对于对照生物膜细胞，7.8-log减少，P ≤ 0.001）。此外，e-支架根除了生物膜中的持留细胞，没有留下活细胞（与对照持留细胞相比减少5个对数，P ≤ 0.001）。结果表明，e-支架诱导细胞内羟基自由基的形成，提高了e-支架处理的生物膜细胞的膜通透性，这可能增强了抗生素敏感性，根除了持留细胞。这些结果证明了e-支架在治疗持续性生物膜感染中的有前途的优势。使用导电织物产生过氧化氢可以根除慢性感染伤口中的持久生物膜。电化学支架（e-支架）是导电材料（如碳纤维）的薄网络，用于在与其接触的介质中产生化学反应。美国华盛顿州立大学的Haluk Beyenal及其同事研究了碳纤维e-支架对铜绿假单胞菌培养生物膜的影响。该过程增强了这种麻烦的多重耐药细菌对抗生素妥布霉素的敏感性。最重要的是，它根除了所谓的持续性细胞，这些细胞可以逃避抗生素治疗，从而改革慢性伤口中的生物膜。研究表明，这种效应涉及过氧化氢产生的羟基自由基和细菌细胞膜渗透性的增加。电子支架治疗感染伤口的潜力值得进一步探索。
Biofilms in chronic wounds are known to contain a persister subpopulation that exhibits enhanced multidrug tolerance and can quickly rebound after therapeutic treatment. The presence of these “persister cells” is partly responsible for the failure of antibiotic therapies and incomplete elimination of biofilms. Electrochemical methods combined with antibiotics have been suggested as an effective alternative for biofilm and persister cell elimination, yet the mechanism of action for improved antibiotic efficacy remains unclear. In this work, an electrochemical scaffold (e-scaffold) that electrochemically generates a constant concentration of H2O2 was investigated as a means of enhancing tobramycin susceptibility in pre-grown Pseudomonas aeruginosa PAO1 biofilms and attacking persister cells. Results showed that the e-scaffold enhanced tobramycin susceptibility in P. aeruginosa PAO1 biofilms, which reached a maximum susceptibility at 40 µg/ml tobramycin, with complete elimination (7.8-log reduction vs control biofilm cells, P ≤ 0.001). Moreover, the e-scaffold eradicated persister cells in biofilms, leaving no viable cells (5-log reduction vs control persister cells, P ≤ 0.001). It was observed that the e-scaffold induced the intracellular formation of hydroxyl free radicals and improved membrane permeability in e-scaffold treated biofilm cells, which possibly enhanced antibiotic susceptibility and eradicated persister cells. These results demonstrate a promising advantage of the e-scaffold in the treatment of persistent biofilm infections. Using an electrically conductive fabric to generate hydrogen peroxide could eradicate persistent biofilms in chronically infected wounds. Electrochemical scaffolds (e-scaffolds) are thin networks of conductive material such as carbon fiber used to generate chemical responses in media they are in contact with. Haluk Beyenal and colleagues at Washington State University, USA, investigated the effect of a carbon fabric e-scaffold on cultured biofilms of the bacterium Pseudomonas aeruginosa. The procedure enhanced the susceptibility of this troublesome multidrug-resistant bacterium to the antibiotic tobramycin. Crucially, it eradicated so-called persister cells that can evade antibiotic treatment to reform biofilms in chronic wounds. The research suggests that the effect involves the production of hydroxyl free radicals from hydrogen peroxide and increased permeability of the bacterial cell membranes. The potential of e-scaffolds for treating infected wounds warrants further exploration.