Biomedical Engineering Institute, Jinan University, Guangzhou 510632, PR China.
Department of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3568 CG Utrecht, the Netherlands.
Carbohydr Polym. 2019 Feb 15;206:653-663. doi: 10.1016/j.carbpol.2018.11.044. Epub 2018 Nov 17.
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.
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。