Morohoshi Tomohiro, Shiono Toshitaka, Takidouchi Kiyomi, Kato Masashi, Kato Norihiro, Kato Junichi, Ikeda Tsukasa
Department of Applied Chemistry, Utsunomiya University, 7-1-2 Yoto, Utsunomiya 321-8585, Japan.
Appl Environ Microbiol. 2007 Oct;73(20):6339-44. doi: 10.1128/AEM.00593-07. Epub 2007 Aug 3.
Quorum sensing is a regulatory system for controlling gene expression in response to increasing cell density. N-Acylhomoserine lactone (AHL) is produced by gram-negative bacteria, which use it as a quorum-sensing signal molecule. Serratia marcescens is a gram-negative opportunistic pathogen which is responsible for an increasing number of serious nosocomial infections. S. marcescens AS-1 produces N-hexanoyl homoserine lactone (C(6)-HSL) and N-(3-oxohexanoyl) homoserine lactone and regulates prodigiosin production, swarming motility, and biofilm formation by AHL-mediated quorum sensing. We synthesized a series of N-acyl cyclopentylamides with acyl chain lengths ranging from 4 to 12 and estimated their inhibitory effects on prodigiosin production in AS-1. One of these molecules, N-nonanoyl-cyclopentylamide (C(9)-CPA), had a strong inhibitory effect on prodigiosin production. C(9)-CPA also inhibited the swarming motility and biofilm formation of AS-1. A competition assay revealed that C(9)-CPA was able to inhibit quorum sensing at four times the concentration of exogenous C(6)-HSL and was more effective than the previously reported halogenated furanone. Our results demonstrated that C(9)-CPA was an effective quorum-sensing inhibitor for S. marcescens AS-1.
群体感应是一种调控系统，用于响应细胞密度增加来控制基因表达。N-酰基高丝氨酸内酯（AHL）由革兰氏阴性菌产生，这些细菌将其用作群体感应信号分子。粘质沙雷氏菌是一种革兰氏阴性机会致病菌，导致越来越多严重的医院感染。粘质沙雷氏菌AS-1产生N-己酰高丝氨酸内酯（C(6)-HSL）和N-(3-氧代己酰基)高丝氨酸内酯，并通过AHL介导的群体感应调节灵菌红素的产生、群体运动性和生物膜形成。我们合成了一系列酰基链长度为4至12的N-酰基环戊酰胺，并评估了它们对AS-1中灵菌红素产生的抑制作用。其中一种分子，N-壬酰基环戊酰胺（C(9)-CPA），对灵菌红素的产生有很强的抑制作用。C(9)-CPA还抑制了AS-1的群体运动性和生物膜形成。竞争试验表明，C(9)-CPA能够在外源C(6)-HSL浓度四倍时抑制群体感应，且比先前报道的卤代呋喃酮更有效。我们的结果表明，C(9)-CPA是粘质沙雷氏菌AS-1的一种有效的群体感应抑制剂。
