Quorum sensing inhibitory activities of surface immobilized antibacterial dihydropyrrolones via click chemistry
Quorum sensing inhibitory activities of surface immobilized antibacterial dihydropyrrolones via click chemistry
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DOI：
10.1016/j.biomaterials.2013.11.072
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发表时间：
2014-02-01
期刊：
影响因子：
14
通讯作者：
Kumar, Naresh
中科院分区：
文献类型：
--
作者：
Ho, Kitty K. K.;Chen, Renxun;Kumar, Naresh
器械相关感染仍然是使用生物材料植入物作为救生器械的主要障碍。本研究旨在探讨表面附着二氢吡咯酮（DHPs），一种群体感应（QS）抑制剂，对细菌定植的有效性和作用机制。DHP通过铜催化的叠氮-炔1，3-偶极环加成（CuAAC）点击反应共价连接在玻璃表面上。通过X射线光电子能谱（XPS）和接触角测量证实了DHP表面的共价连接，并通过共聚焦激光扫描显微镜（CLSM）和图像分析评估了DHP涂层的抗菌功效。结果表明，共价结合的DHP化合物对于铜绿假单胞菌和金黄色葡萄球菌两者都有效地降低粘附高达97%（p < 0.05）。此外，使用基于绿色荧光蛋白（GFP）的报告基因技术，证明了表面附着的DHP能够抑制铜绿假单胞菌lasB-gfp报告基因融合体的表达72%（p < 0.001），而不影响细胞活力。这证明了共价结合的QS抑制剂抑制QS的能力，并表明存在QS抑制的膜基途径。因此，基于掺入QS抑制剂（如DHP）的策略代表了预防器械相关感染的潜在方法。(c)2013爱思唯尔有限公司保留所有权利。
Device-related infection remains a major barrier to the use of biomaterial implants as life-saving devices. This study aims to examine the effectiveness and mechanism of action of surface attached dihydropyrrolones (DHPs), a quorum sensing (QS) inhibitor, against bacterial colonization. DHPs were covalently attached on glass surfaces via copper-catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC) click reaction. The covalent attachment of DHP surfaces was confirmed by X-ray photoelectron spectroscopy (XPS) and contact angle measurements, and the antimicrobial efficacy of the DHP coatings was assessed by confocal laser scanning microscopy (CLSM) and image analysis. The results demonstrated that covalently bound DHP compounds are effective in reducing the adhesion by up to 97% (p < 0.05) for both Pseudomonas aeruginosa and Staphylococcus aureus. Furthermore, using the green fluorescent protein (Gfp)-based reporter technology, it is demonstrated that surface attached DHPs were able to repress the expression of a lasB-gfp reporter fusion of P. aeruginosa by 72% (p < 0.001) without affecting cell viability. This demonstrates the ability of the covalently bound QS inhibitor to inhibit QS and suggests the existence of a membrane-based pathway(s) for QS inhibition. Hence, strategies based on incorporation of QS inhibitors such as DHPs represent a potential approach for prevention of device-related infections. (c) 2013 Elsevier Ltd. All rights reserved.