Pseudomonas aeruginosa is the predominant pathogen in the persistent lung infections of cystic fibrosis (CF) patients among other diseases. One of the mechanisms of resistance of P. aeruginosa infections is the formation and presence of biofilms. Previously, we demonstrated that PEGylated-tobramycin (Tob-PEG) had superior antimicrobial activity against P. aeruginosa biofilms compared to tobramycin (Tob). The goal of this study was to optimize the method of PEGylation of Tob and assess its activity in an in vitro CF-like mucus barrier biofilm model. Tob was PEGylated using three separate chemical conjugation methods and analyzed by ¹H NMR. A comparison of the Tob-PEG products from the different conjugation methods showed significant differences in the reduction of biofilm proliferation after 24 h of treatment. In the CF-like mucus barrier model, Tob-PEG was significantly better than Tob in reducing P. aeruginosa proliferation after only 5 h of treatment (p < 0.01). Finally, Tob-PEG caused a reduction in the number of surviving P. aeruginosa biofilm colonies higher than that of Tob (p < 0.0001). We demonstrate the significantly improved antimicrobial activity of Tob-PEG against P. aeruginosa biofilms compared to Tob using two PEGylation methods. Tob-PEG had better in vitro activity compared to that of Tob against P. aeruginosa biofilms growing in a CF-like mucus barrier model.

中文翻译：

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妥布霉素的聚乙二醇化改善了体外对铜绿假单胞菌生物膜的粘液渗透和抗菌活性。

铜绿假单胞菌是囊性纤维化（CF）患者持续性肺部感染的主要病原体。铜绿假单胞菌感染的抗性机制之一是生物膜的形成和存在。以前，我们证明了与妥布霉素（Tob）相比，聚乙二醇化妥布霉素（Tob-PEG）对铜绿假单胞菌生物膜具有优异的抗菌活性。这项研究的目的是优化Tob的PEG化方法，并在体外CF样粘液屏障生物膜模型中评估其活性。使用三种单独的化学偶联方法将Tob聚乙二醇化，并用¹1 H NMR。对来自不同缀合方法的Tob-PEG产物进行的比较显示，处理24小时后，生物膜增殖的减少存在显着差异。在CF样粘液屏障模型中，Tob-PEG在仅治疗5小时后在减少铜绿假单胞菌增殖方面明显优于Tob （p <0.01）。最后，Tob-PEG导致存活的铜绿假单胞菌生物膜菌落的数量高于Tob（p <0.0001）。我们证明了Tob-PEG对铜绿假单胞菌生物膜的抗微生物活性明显高于使用两种PEG化方法的Tob。与Tob相比，Tob-PEG的体外活性更好铜绿假单胞菌生物膜在CF状粘液屏障模型中生长。