Quinolone signaling in the cell-to-cell communication system of Pseudomonas aeruginosa
Quinolone signaling in the cell-to-cell communication system of Pseudomonas aeruginosa
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DOI：
10.1073/pnas.96.20.11229
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发表时间：
1999-09-28
影响因子：
11.1
通讯作者：
Iglewski, BH
中科院分区：
文献类型：
--
作者：
Pesci, EC;Milbank, JBJ;Iglewski, BH
许多细菌物种使用一种称为群体感应的优雅调节机制，以依赖于细胞密度的方式控制特定基因的表达。在革兰氏阴性细菌中，群体感应系统通过细胞间信号分子（自诱导剂）发挥作用，该信号分子由具有脂肪酸侧链的高丝氨酸内酯组成。机会性人类病原体铜绿假单胞菌就是这种情况，它含有两个群体感应系统（las 和 rhl），通过自诱导剂 N-(3-氧代十二酰基)-L-高丝氨酸内酯和 N-丁酰-L-高丝氨酸内酯发挥作用。对这些信号分子的研究表明，它们结合并激活特异性诱导大量铜绿假单胞菌毒力基因的转录激活蛋白。我们在此报道铜绿假单胞菌产生另一种信号分子，2-庚基-3-羟基-4-喹诺酮，它被指定为假单胞菌喹诺酮信号。研究发现，这种独特的细胞间信号控制着 lasB 的表达，lasB 编码主要毒力因子 LasB 弹性蛋白酶。我们还表明，假单胞菌喹诺酮信号的合成和生物活性分别由铜绿假单胞菌 las 和 rhl 群体感应系统介导。 2-庚基-3-羟基-4-喹诺酮可以充当细胞间信号的证明揭示了次级代谢产物的作用，并表明铜绿假单胞菌细胞间信号传导并不限于酰基高丝氨酸内酯。
Numerous species of bacteria use an elegant regulatory mechanism known as quorum sensing to control the,expression of specific genes in a cell-density dependent manner. In Gram-negative bacteria, quorum sensing systems function through a cell-to-cell signal molecule (autoinducer) that consists of a homoserine lactone with a fatty acid side chain. Such is the case in the opportunistic human pathogen Pseudomonas aeruginosa, which contains two quorum sensing systems (las and rhl) that operate via the autoinducers, N-(3-oxododecanoyl)-L-homoserine lactone and N-butyryl-L-homoserine lactone, The study of these signal molecules has shown that they bind to and activate transcriptional activator proteins that specifically induce numerous P. aeruginosa virulence genes. We report here that P. aeruginosa produces ano ther signal molecule, 2-heptyl-3-hydroxy-4-quinolone, which has been designated as the Pseudomonas quinolone signal. It was found that this unique cell-to-cell signal controlled the expression of lasB, which encodes for the major virulence factor, LasB elastase, We also show that the synthesis and bioactivity of Pseudomonas quinolone signal were mediated by the P. aeruginosa las and rhl quorum sensing systems, respectively. The demonstration that 2-heptyl-3-hydroxy-4-quinolone can function as an intercellular signal sheds light on the role of secondary metabolites and shows that P. aeruginosa cell-to-cell signaling is not restricted to acyl-homoserine lactones.