The Pseudomonas aeruginosa quinolone signal molecule overcomes the cell density-dependency of the quorum sensing hierarchy, regulates rhl-dependent genes at the onset of stationary phase and can be produced in the absence of LasR

The Pseudomonas aeruginosa quinolone signal molecule overcomes the cell density-dependency of the quorum sensing hierarchy, regulates rhl-dependent genes at the onset of stationary phase and can be produced in the absence of LasR
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DOI:
10.1046/j.1365-2958.2003.03672.x
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发表时间:
2003-10-01
影响因子:
3.6
通讯作者:
Williams, P
Williams, P
中科院分区:
生物学2区
文献类型:
--
作者:
Diggle, SP;Winzer, K;Williams, P

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在铜绿假单胞菌中,不同的外源毒力决定因素通过N-酰基高丝氨酸内酯依赖的群体感应来调节。在这里,我们证明了2-庚基-3-羟基-4(1H)-喹诺酮(PQS)也是群体感应电路的一个组成部分,并且是在固定相开始时产生依赖于rhl的外源产物所必需的。对铜绿假单胞菌培养上清液的分析表明,PQS在亲本菌株的对数生长期末期和LasR突变体的稳定期后期产生。PQS产生(PqsR-)和响应(pqsE-)缺陷的突变株产生的外源产物水平大大降低,但保留了野生型N-丁酰高丝氨酸内酯(C4-HSL)的水平。在野生型中,在接种时提供外源PQS显著增加了静止期早期PA-IL凝集素、绿青素和弹性蛋白酶的产量,并促进了生物膜的形成。外源PQS而不是缺少3-羟基的PQS衍生物克服了外源产物的细胞密度,但不能克服外源产物的生长阶段依赖性。PQS还克服了LecA(PA-IL凝集素的编码)分别通过负调控因子MvaT和RSMA介导的转录和转录后抑制。外源PQS诱导的LecA表达增加部分可以通过RhlR、rpos和C4-HSL水平的增加来解释。提出了一种改进的铜绿假单胞菌群体感应模型。
In Pseudomonas aeruginosa, diverse exoproduct virulence determinants are regulated via N-acylhomoserine lactone-dependent quorum sensing. Here we show that 2-heptyl-3-hydroxy-4(1H)-quinolone (PQS) is also an integral component of the quorum sensing circuitry and is required for the production of rhl-dependent exoproducts at the onset of stationary phase. Analysis of spent P. aeruginosa culture supernatants revealed that PQS is produced at the end of exponential phase in the parent strain and in the late stationary phase of a lasR mutant. Mutants defective in both PQS production (pqsR-) and response (pqsE-) produced substantially reduced levels of exoproducts but retained wild-type N-butanoyl homoserine lactone (C4-HSL) levels. In the wild type, provision of exogenous PQS at the time of inoculation significantly increased PA-IL lectin, pyocyanin and elastase production during early stationary phase and promoted biofilm formation. Exogenous PQS but not PQS derivatives lacking the 3-hydroxy group overcame the cell density but not growth phase-dependent production of exoproducts. PQS also overcame the transcriptional and post-transcriptional repression of lecA ( which codes for the PA-IL lectin) mediated via the negative regulators MvaT and RsmA respectively. Increased expression of lecA in the presence of exogenous PQS can be explained partially by increases in RhlR, RpoS and C4-HSL levels. A refined model for quorum sensing in P. aeruginosa is presented.