Combating Pseudomonas aeruginosa Biofilms by a Chitosan-PEG-Peptide Conjugate via Changes in Assembled Structure
Combating Pseudomonas aeruginosa Biofilms by a Chitosan-PEG-Peptide Conjugate via Changes in Assembled Structure
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通过改变组装结构，壳聚糖-PEG-肽缀合物对抗铜绿假单胞菌生物膜
DOI：
10.1021/acsami.0c02034
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发表时间：
2020-03-25
影响因子：
9.5
通讯作者：
Niu, Zhongwei
中科院分区：
文献类型：
--
作者：
Ju, Xiaoyan;Chen, Jun;Niu, Zhongwei
铜绿假单胞菌（P. aeruginosa）生物膜与从慢性组织疾病到植入医疗器械的广泛感染相关。在生物膜中，胞外聚合物（EPS）导致抗菌剂的渗透受到抑制，导致细菌的耐受性增加100-1000倍。针对生物膜中的充水通道和EPS的高负电荷性，本研究设计了一种壳聚糖-聚乙二醇-肽偶联物（CS-PEG-LK 13）。CS-PEG-LK 13在水性环境中偏好大小类似于100 nm的中性电荷组装体，同时经历解体以在细菌细胞膜处暴露α-螺旋肽。这种行为提供了CS-PEG-LK 13在穿透生物膜和灭活细菌方面的优势。在最小抑菌浓度的8倍浓度下，CS-PEG-LK 13在体外铜绿假单胞菌生物膜中具有比LK 13肽（15.24%）和妥布霉素（33.57%）高得多的抗菌效率（72.70%）。此外，CS-PEG-LK 13表现出与高度过量的妥布霉素相当的对抗植入的铜绿假单胞菌生物膜的能力。这项工作的影响，设计新的抗菌剂在生物膜打击。
Pseudomonas aeruginosa (P. aeruginosa) biofilms are associated with a wide range of infections, from chronic tissue diseases to implanted medical devices. In a biofilm, the extracellular polymeric substance (EPS) causes an inhibited penetration of antibacterial agents, leading to a 100-1000 times tolerance of the bacteria. In view of the water-filled channels in biofilms and the highly negative charge of EPS, we design a chitosan-polyethylene glycol-peptide conjugate (CS-PEG-LK13) in this study. The CS-PEG-LK13 prefers a neutrally charged assembly at a size of similar to 100 nm in aqueous environment, while undergoes disassembly to expose the a-helical peptide at the bacterial cell membrane. This behavior provides CS-PEG-LK13 superiorities in both penetrating the biofilms and inactivating the bacteria. At a concentration of 8 times the minimum inhibitory concentration, CS-PEG-LK13 has a much higher antibacterial efficiency (72.70%) than LK13 peptide (15.24%) and tobramycin (33.57%) in an in vitro P. aeruginosa biofilm. Moreover, CS-PEG-LK13 behaves comparable capability of combating an implanted P. aeruginosa biofilm to highly excess tobramycin. This work has implications for the design of new antibacterial agents in biofilm combating.