Furanone derivatives as quorum-sensing antagonists of Pseudomonas aeruginosa
Furanone derivatives as quorum-sensing antagonists of Pseudomonas aeruginosa
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DOI：
10.1007/s00253-008-1474-6
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发表时间：
2008-08-01
影响因子：
5
通讯作者：
Yoon, Jeyong
中科院分区：
文献类型：
--
作者：
Kim, Cheoljin;Kim, Jaeeun;Yoon, Jeyong
铜绿假单胞菌（Pseudomonas aeruginosa）是一种机会性人类病原体，其生物膜的形成是通过细胞间信号传导，即所谓的群体感应（quorum sensing， QS）来实现的。为了控制生物膜的形成，我们在已知QS抑制剂呋喃酮结构的基础上设计并合成了新的QS抑制剂P. aeruginosa。新合成的化合物是一系列（5-氧-2,5-二氢呋喃-3-基）烷酸甲酯的类似物，并通过NMR和GC/MS分析证实了这6个化合物的结构。利用重组报告系统和流式细胞共聚焦显微镜检测了这些新的QS候选抑制剂对假单胞菌QS信号传导和生物膜形成的抑制作用。这些新的抑制剂对QS的抑制程度从20%到90%不等。为了更深入地了解抑制机制，我们尝试从硅模拟系统中估计QS受体、LasR和我们的抑制剂之间的结合能。模型系统预测的结合模式与我们的QS抑制实验数据吻合良好。基于这些结果，我们提出了一种基于结构建模的开发QS抑制剂和生物膜控制剂的新方法。
The biofilm formation of Pseudomonas aeruginosa, an opportunistic human pathogen, is developed by cell-to-cell signaling, so-called quorum sensing (QS). To control the biofilm formation, we designed and synthesized new QS inhibitors of P. aeruginosa based on the structure of the previously known QS inhibitor, furanone. Newly synthesized compounds were a series of analogs of (5-oxo-2,5-dihydrofuran-3-yl)methyl alkanoate, and the structures of all six synthesized compounds was confirmed by NMR and GC/MS analyses. These new QS inhibitor candidates could remarkably inhibit both Pseudomonas QS signaling and biofilm formation, which were assayed by using the recombinant reporter system and flow cell confocal microscopy. The degree of QS inhibition by these new inhibitors varied from 20% to 90%. For the profound understanding about inhibition mechanism, we tried to estimate the binding energy between QS receptor, LasR, and our inhibitors from the in silico modeling system. The predicted binding pattern from the modeling system and our experimental data about QS inhibition were in good agreement. From these results, we suggest a new approach to develop the QS inhibitors and biofilm control agents based on structural modeling.