Inhibition of quorum sensing in Serratia marcescens AS-1 by synthetic analogs of N-acylhomoserine lactone
Inhibition of quorum sensing in Serratia marcescens AS-1 by synthetic analogs of N-acylhomoserine lactone
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DOI：
10.1128/aem.00593-07
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发表时间：
2007-10-01
影响因子：
4.4
通讯作者：
Ikeda, Tsukasa
中科院分区：
文献类型：
--
作者：
Morohoshi, Tornohiro;Shiono, Toshitaka;Ikeda, Tsukasa
群体感应是一种响应细胞密度增加而控制基因表达的调节系统。N-酰基高丝氨酸内酯（N-Acylhomoserine lactone，阿勒）是革兰氏阴性菌产生的一种群体感应信号分子。粘质沙雷氏菌是一种革兰氏阴性的条件致病菌，引起越来越多的严重医院感染。S. marcescens AS-1产生N-己酰基高丝氨酸内酯（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、群集运动性和生物膜形成。我们合成了一系列N-酰基环戊酰胺，酰基链长从4到12不等，并估计其对AS-1中灵菌红素产生的抑制作用。这些分子之一，N-壬酰基-环戊酰胺（C-9-CPA），对灵菌红素的生产有很强的抑制作用。C9-CPA还抑制AS-1的群集运动和生物膜形成。竞争试验表明，C-9-CPA能够抑制群体感应在四倍浓度的外源性C-6-HSL和更有效的比以前报道的卤代呋喃酮。结果表明，C-9-CPA是一种有效的S. marcescens AS-1。
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-nonanoyi-cyclopentylamide (C-9-CPA), had a strong inhibitory effect on prodigiosin production. C9-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.