Du Ju, Bandara H M H N, Du Ping, Huang Hui, Hoang Khang, Nguyen Dang, Mogarala Sri Vasudha, Smyth Hugh D C
†Division of Pharmaceutics, College of Pharmacy, The University of Texas at Austin, Austin, Texas 78712, United States.
‡Division of Medicinal Chemistry, College of Pharmacy, The University of Texas at Austin, Austin, Texas 78712, United States.
Mol Pharm. 2015 May 4;12(5):1544-53. doi: 10.1021/mp500846u. Epub 2015 Apr 2.
The objective of this study was to develop a functionally enhanced antibiotic that would improve the therapeutic activity against bacterial biofilms. Tobramycin was chemically conjugated with polyethylene glycol (PEG) via site-specific conjugation to form PEGylated-tobramycin (Tob-PEG). The antibacterial efficacy of Tob-PEG, as compared to tobramycin, was assessed on the planktonic phase and biofilms phase of Pseudomonas aeruginosa. The minimum inhibitory concentration (MIC80) of Tob-PEG was higher (13.9 μmol/L) than that of tobramycin (1.4 μmol/L) in the planktonic phases. In contrast, the Tob-PEG was approximately 3.2-fold more effective in eliminating bacterial biofilms than tobramycin. Specifically, Tob-PEG had a MIC80 lower than those exhibited by tobramycin (27.8 μmol/L vs 89.8 μmol/L). Both confocal laser scanning microscopy and scanning electron microscopy further confirmed these data. Thus, modification of antimicrobials by PEGylation appears to be a promising approach for overcoming the bacterial resistance in the established biofilms of Pseudomonas aeruginosa.
本研究的目的是开发一种功能增强的抗生素，以提高对细菌生物膜的治疗活性。妥布霉素通过位点特异性共轭与聚乙二醇（PEG）化学结合，形成聚乙二醇化妥布霉素（Tob-PEG）。与妥布霉素相比，在铜绿假单胞菌的浮游菌阶段和生物膜阶段评估了Tob-PEG的抗菌效果。在浮游菌阶段，Tob-PEG的最低抑菌浓度（MIC80）（13.9 μmol/L）高于妥布霉素（1.4 μmol/L）。相比之下，Tob-PEG在消除细菌生物膜方面比妥布霉素有效约3.2倍。具体而言，Tob-PEG的MIC80低于妥布霉素（27.8 μmol/L对89.8 μmol/L）。共聚焦激光扫描显微镜和扫描电子显微镜均进一步证实了这些数据。因此，通过聚乙二醇化修饰抗菌剂似乎是克服铜绿假单胞菌已形成生物膜中细菌耐药性的一种有前景的方法。
