Mattmann Margrith E, Geske Grant D, Worzalla Gregory A, Chandler Josephine R, Sappington Kaia J, Greenberg E Peter, Blackwell Helen E
Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, WI 53706-1322, USA.
Bioorg Med Chem Lett. 2008 May 15;18(10):3072-5. doi: 10.1016/j.bmcl.2007.11.095. Epub 2007 Nov 28.
The transcription factor QscR is a regulator of quorum sensing in Pseudomonas aeruginosa and plays a role in controlling virulence in this prevalent opportunistic pathogen. This study outlines the discovery of a set of synthetic N-acylated homoserine lactones that are capable of either activating or strongly inhibiting QscR in a cell-based reporter gene assay. We demonstrate that the synthetic antagonists inhibit ligand-dependent QscR binding to DNA. Several of these ligands can selectively modulate QscR instead of LasR, or modulate the activity of both receptors, and represent new chemical tools to study the hierarchy of quorum-sensing signaling in P. aeruginosa.
转录因子QscR是铜绿假单胞菌群体感应的调节因子，在控制这种常见的机会致病菌的毒力方面发挥作用。本研究概述了一组合成的N-酰基高丝氨酸内酯的发现，这些内酯在基于细胞的报告基因分析中能够激活或强烈抑制QscR。我们证明，合成拮抗剂抑制配体依赖性QscR与DNA的结合。其中几种配体可以选择性地调节QscR而非LasR，或调节两种受体的活性，并且代表了研究铜绿假单胞菌群体感应信号层次的新化学工具。
