BACKGROUND Novel methods are necessary to reduce morbidity and mortality of patients suffering from infections with Pseudomonas aeruginosa. Being the most common infectious species of the Pseudomonas genus, P. aeruginosa is the primary Gram-negative etiology responsible for nosocomial infections. Due to the ubiquity and high adaptability of this species, an effective universal treatment method for P. aeruginosa infection still eludes investigators, despite the extensive research in this area. RESULTS We report bacterial inhibition by iron-oxide (nominally magnetite) nanoparticles (NPs) alone, having a mean hydrodynamic diameter of ~ 16 nm, as well as alginate-capped iron-oxide NPs. Alginate capping increased the average hydrodynamic diameter to ~ 230 nm. We also investigated alginate-capped iron-oxide NP-drug conjugates, with a practically unchanged hydrodynamic diameter of ~ 232 nm. Susceptibility and minimum inhibitory concentration (MIC) of the NPs, NP-tobramycin conjugates, and tobramycin alone were determined in the PAO1 bacterial colonies. Investigations into susceptibility using the disk diffusion method were done after 3 days of biofilm growth and after 60 days of growth. MIC of all compounds of interest was determined after 60-days of growth, to ensure thorough establishment of biofilm colonies. CONCLUSIONS Positive inhibition is reported for uncapped and alginate-capped iron-oxide NPs, and the corresponding MICs are presented. We report zero susceptibility to iron-oxide NPs capped with polyethylene glycol, suggesting that the capping agent plays a major role in enabling bactericidal ability in of the nanocomposite. Our findings suggest that the alginate-coated nanocomposites investigated in this study have the potential to overcome the bacterial biofilm barrier. Magnetic field application increases the action, likely via enhanced diffusion of the iron-oxide NPs and NP-drug conjugates through mucin and alginate barriers, which are characteristic of cystic-fibrosis respiratory infections. We demonstrate that iron-oxide NPs coated with alginate, as well as alginate-coated magnetite-tobramycin conjugates inhibit P. aeruginosa growth and biofilm formation in established colonies. We have also determined that susceptibility to tobramycin decreases for longer culture times. However, susceptibility to the iron-oxide NP compounds did not demonstrate any comparable decrease with increasing culture time. These findings imply that iron-oxide NPs are promising lower-cost alternatives to silver NPs in antibacterial coatings, solutions, and drugs, as well as other applications in which microbial abolition or infestation prevention is sought.

中文翻译：

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氧化铁，氮化铁和妥布霉素共轭的纳米颗粒对铜绿假单胞菌生物膜的抗菌活性。

背景技术新颖的方法对于减少患有铜绿假单胞菌感染的患者的发病率和死亡率是必要的。铜绿假单胞菌是假单胞菌属最常见的感染物种，是引起医院感染的主要革兰氏阴性病因。由于该物种的普遍存在和高度的适应性，尽管在该领域进行了广泛的研究，但对于铜绿假单胞菌感染的有效的通用治疗方法仍未引起研究者的重视。结果我们报道了平均水动力直径约为16 nm的氧化铁（名义磁铁矿）纳米颗粒（NPs）以及藻酸盐封端的氧化铁NPs对细菌的抑制作用。藻酸盐封端将平均流体动力学直径增加至〜230 nm。我们还研究了藻酸盐封端的氧化铁NP-药物偶联物，具有约232 nm的几乎不变的流体力学直径。测定了PAO1细菌菌落中NP，NP-妥布霉素结合物和妥布霉素的敏感性和最低抑菌浓度（MIC）。在生物膜生长3天后和生长60天后，使用圆盘扩散法对药敏性进行了研究。生长60天后确定所有目标化合物的MIC，以确保彻底建立生物膜集落。结论据报道，对未封端和藻酸盐封端的氧化铁NPs有正抑制作用，并给出了相应的MIC。我们报告对用聚乙二醇封端的氧化铁NPs的敏感性为零，这表明封端剂在使纳米复合材料具有杀菌能力方面起着主要作用。我们的发现表明，在这项研究中研究的藻酸盐涂层纳米复合材料具有克服细菌生物膜屏障的潜力。施加磁场可能会增强作用，可能是通过粘蛋白和藻酸盐屏障增强了氧化铁NP和NP-药物偶联物的扩散，这是囊性纤维化呼吸道感染的特征。我们证明藻酸盐，以及藻酸盐涂层磁铁矿-妥布霉素共轭物的氧化铁NPs抑制铜绿假单胞菌生长和建立的殖民地的生物膜形成。我们还确定，较长的培养时间对妥布霉素的敏感性降低。但是，对氧化铁NP化合物的敏感性并未显示出随着培养时间的增加而发生的任何可比的降低。