Inhibition of quorum sensing in Pseudomonas aeruginosa by N-acyl cyclopentylamides
Inhibition of quorum sensing in Pseudomonas aeruginosa by N-acyl cyclopentylamides
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DOI：
10.1128/aem.02233-06
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发表时间：
2007-05-01
影响因子：
4.4
通讯作者：
Kato, Junichi
中科院分区：
文献类型：
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作者：
Ishida, Takenori;Ikeda, Tsukasa;Kato, Junichi
n -辛烷基环戊酰胺（C8-CPA）适度抑制铜绿假单胞菌PAO1的群体感应。为了获得更有效的抑制剂，我们合成了一系列C8-CPA的结构类似物，并检测了它们抑制P. aeruginosa PAO1群体感应的能力。lasB-lacZ和rhl4-lacZ报告基因分析表明，链长度和环结构对C8-CPA类似物抑制群体感应至关重要。N-Decanoyl cyclopentylamide （C10-CPA）是最强的抑制剂，对lasB-lacZ和rhL4-lacZ表达达到半最大抑制所需的浓度分别为80 μ M和90 μ M。C10-CPA还能抑制弹性酶、花青素和鼠李糖脂等毒力因子的产生和生物膜的形成，但不影响P. aeruginosa PAO1的生长。在铜绿假单胞菌PAO1 lasI rhlI突变体中，C10-CPA抑制N-（3-氧十二烷基）- l-高丝氨酸内酯（PAI1）诱导lasI- lacz和N-丁醇-l -高丝氨酸内酯（PAI2）诱导rhL4-lacZ，表明C10-CPA通过抑制其反应调节因子（LasR和RhIR）与自诱导剂之间的相互作用干扰las和rhl群体感应系统。
N-Octanoyl cyclopentylamide (C8-CPA) was found to moderately inhibit quorum sensing in Pseudomonas aeruginosa PAO1. To obtain more powerful inhibitors, a series of structural analogs of C8-CPA were synthesized and examined for their ability to inhibit quorum sensing in P. aeruginosa PAO1. The lasB-lacZ and rhl4-lacZ reporter assays revealed that the chain length and the ring structure were critical for C8-CPA analogs to inhibit quorum sensing. N-Decanoyl cyclopentylamide (C10-CPA) was found to be the strongest inhibitor, and its concentrations required for half-maximal inhibition for lasB-lacZ and rhL4-lacZ expression were 80 and 90 mu M, respectively. C10-CPA also inhibited production of virulence factors, including elastase, pyocyanin, and rhamnolipid, and biofilm formation without affecting growth of P. aeruginosa PAO1. C10-CPA inhibited induction of both lasI-lacZ by N-(3-oxododecanoyl)-L-homoserine lactone (PAI1) and rhL4-lacZ by N-butanoyl-L-homoserine lactone (PAI2) in the lasI rhlI mutant of P. aeruginosa PAO1, indicating that C10-CPA interferes with the las and rhl quorum-sensing systems via inhibiting interaction between their response regulators (LasR and RhIR) and autoinducers.