School of Chemistry, University of New South Wales, Sydney, NSW 2052, Australia.
School of Optometry and Vision Science, University of New South Wales, Sydney, NSW 2052, Australia.
Biomaterials. 2014 Feb;35(7):2336-45. doi: 10.1016/j.biomaterials.2013.11.072. Epub 2013 Dec 15.
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.
器械相关感染仍然是生物材料植入物作为救生设备使用的主要障碍。本研究旨在研究表面附着的二氢吡咯酮（DHP），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 通过铜催化的叠氮化物-炔烃 1,3-偶极环加成（CuAAC）点击反应共价附着在玻璃表面上。X 射线光电子能谱（XPS）和接触角测量证实了 DHP 表面的共价附着，并用共聚焦激光扫描显微镜（CLSM）和图像分析评估了 DHP 涂层的抗菌效果。结果表明，共价结合的 DHP 化合物可有效减少多达 97%（p < 0.05）的铜绿假单胞菌和金黄色葡萄球菌的粘附。此外，使用绿色荧光蛋白（GFP）报告基因技术，证明表面附着的 DHP 能够抑制铜绿假单胞菌的 lasB-gfp 报告基因融合的表达，抑制率为 72%（p < 0.001），而不影响细胞活力。这表明共价结合的 QS 抑制剂能够抑制 QS，并表明存在基于膜的 QS 抑制途径。因此，基于整合 QS 抑制剂（如 DHP）的策略代表了预防器械相关感染的一种潜在方法。
