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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >MULTIPLE N-ACYL-L-HOMOSERINE LACTONE SIGNAL MOLECULES REGULATE PRODUCTION OF VIRULENCE DETERMINANTS AND SECONDARY METABOLITES IN PSEUDOMONAS AERUGINOSA
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MULTIPLE N-ACYL-L-HOMOSERINE LACTONE SIGNAL MOLECULES REGULATE PRODUCTION OF VIRULENCE DETERMINANTS AND SECONDARY METABOLITES IN PSEUDOMONAS AERUGINOSA

机译：铜绿假单胞菌中多种N-酰基-L-高丝氨酸内酯信号分子调节毒力测定因子和次级代谢产物的产生

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Pseudomonas aeruginosa produces a spectrum of exoproducts many of which have been implicated in the pathogenesis of human infection, Expression of some of these factors requires cell-cell communication involving the interaction of a small diffusible molecule, an ''autoinducer,'' with a positive transcriptional activator, In P. aeruginosa PAO1, LasI directs the synthesis of the autoinducer N-(3-oxododecanoyl)-L-homoserine lactone (OdDHL), which activates the positive transcriptional activator, LasR, Recently, we have discovered a second signaling molecule-based modulon in PAO1, termed vsm, which contains the genes vsmR and vsmI. Using HPLC, mass spectrometry, and NMR spectroscopy we now establish that in Escherichia coli, VsmI directs the synthesis of N-butanoyl-L-homoserine lactone (BHL) and N-hexanoyl-L-homoserine lactone (WWL). These compounds are present in the spent culture supernatants of P, aeruginosa in a molar ratio of approximate to 15:1 and their structures were unequivocally confirmed by chemical synthesis, Addition of either BHL or HHL to PAN067, a pleiotropic P, aeruginosa mutant unable to synthesize either of these autoinducers, restored elastase, chitinase, and cyanide production. In E. coli carrying a vsmR/vsmI'::lux transcriptional fusion, BHL and HHL activated VsmR to a similar extent. Analogues of these N-acyl-L-homoserine lactones in which the N-acyl side chain has been extended and/or oxidized at the C-3 position exhibit substantially lower activity (e.g., OdDHL) or no activity (e.g., dDHL) in this fur reporter assay, These data indicate that multiple families of quorum sensing modulons interactively regulate gene expression in P. aeruginosa. [References: 36]
机译：铜绿假单胞菌产生一系列外生产物，其中许多与人类感染的发病机制有关。其中某些因子的表达需要细胞间的通讯，包括一个小的可扩散分子（一种“自诱导物”）与阳性分子的相互作用。转录激活因子，在铜绿假单胞菌PAO1中，LasI指导自动诱导剂N-（3-氧十二烷酰基）-L-高丝氨酸内酯（OdDHL）的合成，该激活剂激活了积极的转录激活因子LasR，最近，我们发现了第二个信号分子PAO1中基于基因的调节子，称为vsm，其中包含基因vsmR和vsmI。现在，我们使用HPLC，质谱和NMR光谱确定了VsmI指导N-丁酰基-L-高丝氨酸内酯（BHL）和N-己酰基-L-高丝氨酸内酯（WWL）的合成。这些化合物以约15：1的摩尔比存在于铜绿假单胞菌的废培养上清液中，并且通过化学合成明确地确认了它们的结构，将BHL或HHL添加到PAN067中，多效P铜绿假单胞菌突变体不能合成这些自动诱导剂中的任何一种，恢复弹性蛋白酶，几丁质酶和氰化物的产生。在携带vsmR / vsmI':: lux转录融合的大肠杆菌中，BHL和HHL激活VsmR的程度相似。这些N-酰基侧链已在C-3位置被延长和/或氧化的N-酰基-L-高丝氨酸内酯的类似物显示出较低的活性（例如，OdDHL）或无活性（例如，dDHL）。这些数据表明，群体感应模块的多个家族相互作用地调节铜绿假单胞菌中的基因表达。 [参考：36]

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