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LED 209 共轭壳聚糖作为一种选择性抗菌和潜在的抗粘连材料。

LED 209 conjugated chitosan as a selective antimicrobial and potential anti-adhesion material.

机构信息

Biomedical Engineering Institute, Jinan University, Guangzhou 510632, PR China.

Department of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3568 CG Utrecht, the Netherlands.

出版信息

Carbohydr Polym. 2019 Feb 15;206:653-663. doi: 10.1016/j.carbpol.2018.11.044. Epub 2018 Nov 17.

Abstract

The rapid emergence of antibiotic-resistant Gram-negative bacteria (GNB) is becoming a global healthcare concern, and it urgently needs novel strategies to match the clinical challenge. In this work, we conjugated chitosan (CS) with LED 209, a highly selective inhibitor of QseC of GNB, to create the novel selective antimicrobial agent CS/LED. The data of FT-IR, NMR and elemental analysis for CS/LED conjugates proved the successful conjugation of CS with LED 209. Interestingly, the fluorescence signal detected in MDR-E. coli of CS/LED-FITC was about 2 times than that of CS-FITC at 3 h. The results shown that compared with CS, CS/LED exhibited higher selective antimicrobial on MDR-E. coli. Moreover, CS/LED exhibited the lower selectivity and cytotoxicity to mammalian cell than CS. Additionally, an unexpected enhancement of anti-adhesion activity against MDR-E. coli was determined by cellulose membrane coating CS/LED. The results demonstrated that CS/LED could reduce the adhesion of bacteria to the cellulose membrane by about 67.8%, while CS only reduced by about 45.3%. The dressings coated with CS/LED possessed the stronger ability to prevent microbial adhesion compared to the CS-coated dressing. Our present work firstly demonstrated that CS/LED had a highly selective activity and anti-adhesion activity against MDR-E. coli, which offered a potent and selective antimicrobial for combating multidrug-resistant GNB infections.

摘要

快速出现的抗生素耐药革兰氏阴性菌(GNB)正成为全球医疗保健关注的问题,迫切需要新的策略来应对临床挑战。在这项工作中,我们将壳聚糖(CS)与 GNB 的 QseC 高度选择性抑制剂 LED 209 缀合,创造了新型选择性抗菌剂 CS/LED。CS/LED 缀合物的 FT-IR、NMR 和元素分析数据证明了 CS 与 LED 209 的成功缀合。有趣的是,在 3 小时时,CS/LED-FITC 在 MDR-E.coli 中检测到的荧光信号约为 CS-FITC 的 2 倍。结果表明,与 CS 相比,CS/LED 对 MDR-E.coli 表现出更高的选择性抗菌作用。此外,CS/LED 对哺乳动物细胞的选择性和细胞毒性低于 CS。此外,通过纤维素膜涂覆 CS/LED 确定了对 MDR-E.coli 的抗粘附活性的意外增强。结果表明,CS/LED 可使细菌对纤维素膜的粘附减少约 67.8%,而 CS 仅减少约 45.3%。与 CS 涂层敷料相比,涂覆有 CS/LED 的敷料具有更强的防止微生物粘附的能力。我们的工作首次证明,CS/LED 对 MDR-E.coli 具有高度选择性的活性和抗粘附活性,为对抗多药耐药 GNB 感染提供了一种有效且选择性的抗菌剂。

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