A quorum sensing-associated virulence gene of Pseudomonas aeruginosa encodes a LysR-like transcription regulator with a unique self-regulatory mechanism
A quorum sensing-associated virulence gene of Pseudomonas aeruginosa encodes a LysR-like transcription regulator with a unique self-regulatory mechanism
复制标题
DOI：
10.1073/pnas.251465298
复制
发表时间：
2001-12-04
影响因子：
11.1
通讯作者：
Rahme, LG
中科院分区：
文献类型：
--
作者：
Cao, H;Krishnan, G;Rahme, LG
人类条件致病菌铜绿假单胞菌菌株PA 14感染植物和动物。以前，使用植物直接筛选铜绿假单胞菌毒力减弱的突变体，我们确定了一个基因座，pho 34 B12，在哺乳动物的发病机制有关。在此，在pho 34 B12基因座中鉴定的两个相反DRF中的无义点突变揭示了其中之一mvfR（多毒力因子调节器）能够控制突变体phoA 34 B12显示的所有表型。遗传和生物化学证据均表明，mvfR基因编码LysR样转录因子，其正调控弹性蛋白酶、磷脂酶和自诱导物3-氧代-十二烷酰基高丝氨酸内酯（派）和2-庚基-3-羟基-4-喹诺酮（PQS）的产生，以及参与吩嗪生物合成的phnAB操纵子的表达。我们证明，MvfR蛋白是膜相关的，并作为一个转录激活因子，直到细胞达到稳定期，当一个独特的负反馈机制被激活的信号下调的MvfR蛋白。这项工作揭示了铜绿假单胞菌前所未有的毒力机制，并确定了铜绿假单胞菌群体感应级联中一个独特的不可或缺的参与者。
The human opportunistic pathogen Pseudomonas aeruginosa strain PA14 infects both plants and animals. Previously, using plants to screen directly for P. aeruginosa virulence-attenuated mutants, we identified a locus, pho34B12, relevant in mammalian pathogenesis. Here, nonsense point mutations in the two opposing DRFs identified in the pho34B12 locus revealed that one of them, mvfR (multiple virulence factor Regulator), is able to control all of the phenotypes that mutant phoA34B12 displays. Both genetic and biochemical evidence demonstrate that the mvfR gene encodes a LysR-like transcriptional factor that positively regulates the production of elastase, phospholipase, and of the autoinducers, 3-oxo-dodecanoyl homoserine lactone (PAI I) and 2-heptyl-3-hydroxy-4-quinolone (PQS), as well as the expression of the phnAB operon, involved in phenazine biosynthesis. We demonstrate that the MvfR protein is membrane-associated and acts as a transcriptional activator until cells reach stationary phase, when a unique negative feedback mechanism is activated to signal the downregulation of the MvfR protein. This work reveals an unprecedented virulence mechanism of P. aeruginosa and identifies a unique indispensable player in the P, aeruginosa quorum-sensing cascade.