Two distinct pathways supply anthranilate as a precursor of the Pseudomonas quinolone signal
Two distinct pathways supply anthranilate as a precursor of the Pseudomonas quinolone signal
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DOI：
10.1128/jb.00209-07
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发表时间：
2007-05-01
影响因子：
3.2
通讯作者：
Pesci, Everett C.
中科院分区：
文献类型：
--
作者：
Farrow, John M., III;Pesci, Everett C.
铜绿假单胞菌是一种机会性病原体，可在免疫功能低下的患者和囊性纤维化患者中引起严重感染。这种革兰氏阴性细菌使用多种细胞间信号来控制多种细胞功能和毒力。其中一个信号是2-庚基-3-羟基-4-喹诺酮，称为假单胞菌喹诺酮信号(PQS)。该信号作为转录调节因子(PqsR)的共诱导物，积极控制多个毒力基因及其自身的合成。在多种感染模式中，PQS的产生是毒力所必需的，已有研究表明，在感染铜绿假单胞菌的CF患者的肺中也产生了PQS。合成PQS的前体化合物之一是代谢物邻氨基苯甲酸酯。这种化合物可以通过邻氨基苯甲酸酯合成酶将分支酸转化为邻氨基苯甲酸酯，或者通过犬尿氨酸途径的邻氨基苯甲酸酯分支降解色氨酸而得到。在这项研究中，我们提供了有助于确定铜绿假单胞菌中犬尿氨酸途径的数据，并表明犬尿氨酸途径是邻氨基苯甲酸酯合成PQS的关键来源。我们还表明，KYN途径基因是在生长过程中被色氨酸诱导的，并且它们是由犬尿氨酸自动调节的。这项研究为了解铜绿假单胞菌如何产生邻氨基苯甲酸酯提供了坚实的基础，邻氨基苯甲酸酯是PQS和其他4-喹诺酮类药物的前体。
Pseudomonas aeruginosa is an opportunistic pathogen that causes serious infections in immunocompromised patients and those with cystic fibrosis (CF). This gram-negative bacterium uses multiple cell-to-cell signals to control numerous cellular functions and virulence. One of these signals is 2-heptyl-3-hydroxy-4-quinolone, which is referred to as the Pseudomonas quinolone signal (PQS). This signal functions as a coinducer for a transcriptional regulator (PqsR) to positively control multiple virulence genes and its own synthesis. PQS production is required for virulence in multiple models of infection, and it has been shown to be produced in the lungs of CF patients infected by P. aeruginosa. One of the precursor compounds from which PQS is synthesized is the metabolite anthranilate. This compound can be derived from the conversion of chorismate to anthranilate by an anthranilate synthase or through the degradation of tryptophan via the anthranilate branch of the kynurenine pathway. In this study, we present data which help to define the kynurenine pathway in P. aeruginosa and show that the kynurenine pathway serves as a critical source of anthranilate for PQS synthesis. We also show that the kyn pathway genes are induced during growth with tryptophan and that they are autoregulated by kynurenine. This study provides solid foundations for the understanding of how P. aeruginosa produces the anthranilate that serves as a precursor to PQS and other 4-quinolones.