Department of Systems Biology, Technical University of Denmark, Kongens Lyngby, 2800, Denmark.
Molecules. 2010 Feb 3;15(2):780-92. doi: 10.3390/molecules15020780.
Pseudomonas aeruginosa is an opportunistic pathogen which is responsible for a wide range of infections. Production of virulence factors and biofilm formation by P. aeruginosa are partly regulated by cell-to-cell communication quorum-sensing systems. Identification of quorum-quenching reagents which block the quorum-sensing process can facilitate development of novel treatment strategies for P. aeruginosa infections. We have used molecular dynamics simulation and experimental studies to elucidate the efficiencies of two potential quorum-quenching reagents, triclosan and green tea epigallocatechin gallate (EGCG), which both function as inhibitors of the enoyl-acyl carrier protein (ACP) reductase (ENR) from the bacterial type II fatty acid synthesis pathway. Our studies suggest that EGCG has a higher binding affinity towards ENR of P. aeruginosa and is an efficient quorum-quenching reagent. EGCG treatment was further shown to be able to attenuate the production of virulence factors and biofilm formation of P. aeruginosa.
铜绿假单胞菌是一种机会性病原体，可导致多种感染。铜绿假单胞菌毒力因子的产生和生物膜的形成部分受到细胞间通讯群体感应系统的调节。鉴定阻断群体感应过程的群体感应淬灭试剂可以促进开发治疗铜绿假单胞菌感染的新策略。我们使用分子动力学模拟和实验研究阐明了两种潜在的群体感应淬灭试剂三氯生和绿茶表没食子儿茶素没食子酸酯（EGCG）的效率，它们都作为细菌 II 型脂肪酸合成途径中的酰基辅酶 A 还原酶（ENR）抑制剂发挥作用。我们的研究表明，EGCG 对铜绿假单胞菌的 ENR 具有更高的结合亲和力，并且是一种有效的群体感应淬灭试剂。EGCG 处理进一步显示能够减弱铜绿假单胞菌毒力因子的产生和生物膜的形成。
