The PqsE and RhlR proteins are an autoinducer synthase-receptor pair that control virulence and biofilm development in Pseudomonas aeruginosa.
The PqsE and RhlR proteins are an autoinducer synthase-receptor pair that control virulence and biofilm development in Pseudomonas aeruginosa.
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DOI：
10.1073/pnas.1814023115
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发表时间：
2018-10-02
影响因子：
11.1
通讯作者：
Bassler BL
中科院分区：
文献类型：
--
作者：
Mukherjee S;Moustafa DA;Stergioula V;Smith CD;Goldberg JB;Bassler BL
人类病原体铜绿假单胞菌是医院获得性感染的主要原因，而且对常用的抗生素具有耐药性。铜绿假单胞菌使用称为群体感应（QS）的细胞间通讯过程来控制毒力。QS依赖于对称为自身诱导物的细胞外信号分子的产生和应答。在这里，我们确定的PqsE酶的自诱导物，激活QS受体RhlR的合酶。我们表明，PqsE衍生的自诱导物是驱动铜绿假单胞菌生物膜形成和动物感染模型中的毒力的关键分子。我们认为PqsE和RhlR构成了一个QS酶-受体对，并且该系统可以作为抗菌剂开发的目标。铜绿假单胞菌是危及生命的医院感染的主要原因。由铜绿假单胞菌产生的许多毒力因子由称为群体感应（QS）的细胞间通信过程控制。QS依赖于合成、释放和对称为自身诱导物的细胞外信号分子的群体反应。铜绿假单胞菌具有两个典型的LuxI/R型QS系统，LasI/R和RhlI/R，分别产生和检测3OC12-高丝氨酸内酯和C4-高丝氨酸内酯。以前，我们发现，RhlR调节RhlI依赖和RhlI独立的调节子，我们提出了一种替代配体功能与RhlR一起控制靶基因在RhlI的情况下。在这里，我们报告的酶，PqsE，这是替代配体合成酶的鉴定。使用生物膜分析，报告分析，定点诱变，蛋白质生物化学，和动物感染的研究，我们表明，PqsE产生的替代配体是关键的自诱导物，促进毒力基因的表达。因此，PqsE可以作为治疗干预的靶点。此外，这项工作表明，PqsE和RhlR的功能作为一个QS-自诱导剂的辅酶A酶受体对，驱动群体行为的铜绿假单胞菌。
The human pathogen Pseudomonas aeruginosa is the leading cause of hospital-acquired infections and, moreover, is resistant to commonly used antibiotics. P. aeruginosa uses the cell-to-cell communication process called quorum sensing (QS) to control virulence. QS relies on production and response to extracellular signaling molecules called autoinducers. Here, we identify the PqsE enzyme as the synthase of an autoinducer that activates the QS receptor RhlR. We show that the PqsE-derived autoinducer is the key molecule driving P. aeruginosa biofilm formation and virulence in animal models of infection. We propose that PqsE and RhlR constitute a QS synthase–receptor pair, and that this system can be targeted for antimicrobial development. Pseudomonas aeruginosa is a leading cause of life-threatening nosocomial infections. Many virulence factors produced by P. aeruginosa are controlled by the cell-to-cell communication process called quorum sensing (QS). QS depends on the synthesis, release, and groupwide response to extracellular signaling molecules called autoinducers. P. aeruginosa possesses two canonical LuxI/R-type QS systems, LasI/R and RhlI/R, that produce and detect 3OC12-homoserine lactone and C4-homoserine lactone, respectively. Previously, we discovered that RhlR regulates both RhlI-dependent and RhlI-independent regulons, and we proposed that an alternative ligand functions together with RhlR to control the target genes in the absence of RhlI. Here, we report the identification of an enzyme, PqsE, which is the alternative-ligand synthase. Using biofilm analyses, reporter assays, site-directed mutagenesis, protein biochemistry, and animal infection studies, we show that the PqsE-produced alternative ligand is the key autoinducer that promotes virulence gene expression. Thus, PqsE can be targeted for therapeutic intervention. Furthermore, this work shows that PqsE and RhlR function as a QS-autoinducer synthase–receptor pair that drives group behaviors in P. aeruginosa.
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影响因子：
6.7
作者：
Hazan R;He J;Xiao G;Dekimpe V;Apidianakis Y;Lesic B;Astrakas C;Déziel E;Lépine F;Rahme LG
通讯作者：
Rahme LG
影响因子：
3.2
作者：
BRINT, JM;OHMAN, DE
通讯作者：
OHMAN, DE
影响因子：
14.8
作者：
Kelley LA;Mezulis S;Yates CM;Wass MN;Sternberg MJ
通讯作者：
Sternberg MJ
DOI：
10.1099/00221287-146-10-2469
发表时间：
2000-10-01
期刊：
MICROBIOLOGY-UK
影响因子：
--
作者：
Laue, RE;Jiang, Y;Williams, P
通讯作者：
Williams, P
影响因子：
3.2
作者：
Duerkop, Breck A.;Ulrich, Ricky L.;Greenberg, E. Peter
通讯作者：
Greenberg, E. Peter