The Pseudomonas aeruginosa Orphan Quorum Sensing Signal Receptor QscR Regulates Global Quorum Sensing Gene Expression by Activating a Single Linked Operon.
The Pseudomonas aeruginosa Orphan Quorum Sensing Signal Receptor QscR Regulates Global Quorum Sensing Gene Expression by Activating a Single Linked Operon.
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DOI：
10.1128/mbio.01274-18
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发表时间：
2018-08-28
期刊：
影响因子：
6.4
通讯作者：
Dandekar AA
中科院分区：
文献类型：
--
作者：
Ding F;Oinuma KI;Smalley NE;Schaefer AL;Hamwy O;Greenberg EP;Dandekar AA
铜绿假单胞菌使用两个酰基高丝氨酸内酯信号和两个群体感应（QS）转录因子LasR和RhlR来激活数十个基因。LasR响应于N-3-氧代-十二烷酰基-高丝氨酸内酯（3 OC 12-HSL），RhIR响应于N-丁酰基-高丝氨酸内酯（C4-HSL）。存在第三种铜绿假单胞菌酰基-高丝氨酸-内酯响应性转录因子QscR，其通过未知机制抑制或延迟LasR和RhlR对基因的激活。为了更好地理解QscR在铜绿假单胞菌QS中的作用，我们进行了染色质免疫沉淀分析，其显示该转录因子仅结合与qscR（PA 1895至PA 1897）相连的三个基因的单个操纵子的启动子。在转录组研究中似乎受QscR调控的其他基因不是QscR的直接靶点。PA 1897的缺失重现了QscR无效突变体的早期QS激活表型，并且QscR无效突变体的表型被PA 1895 -1897补充，但不是单独被PA 1897补充。我们的结论是，QscR行为调制群体感应通过调节一个单一的操纵子，显然提高了QS阈值的人口和提供了一个“刹车”的QS自诱导。群体感应是一种细胞间通讯系统，广泛分布于细菌中，通常用于调节共享产物的产生。群体感应的一个重要结果是延迟某些产品的生产，直到人口密度高。铜绿假单胞菌有一个特别复杂的群体感应系统，涉及多种信号和受体。这些受体之一，QscR，下调基因表达，不同于铜绿假单胞菌中的其他受体。QscR通过诱导单个操纵子的表达来实现这一点，该操纵子的功能提供了对达到法定量的群体的抗性元素。这一发现对群体感应抑制策略的设计具有重要意义，也可以为使用群体感应受体调节基因表达的合成生物回路的设计提供信息。
Pseudomonas aeruginosa uses two acyl-homoserine lactone signals and two quorum sensing (QS) transcription factors, LasR and RhlR, to activate dozens of genes. LasR responds to N-3-oxo-dodecanoyl-homoserine lactone (3OC12-HSL) and RhlR to N-butanoyl-homoserine lactone (C4-HSL). There is a third P. aeruginosa acyl-homoserine-lactone-responsive transcription factor, QscR, which acts to dampen or delay activation of genes by LasR and RhlR by an unknown mechanism. To better understand the role of QscR in P. aeruginosa QS, we performed a chromatin immunoprecipitation analysis, which showed this transcription factor bound the promoter of only a single operon of three genes linked to qscR, PA1895 to PA1897. Other genes that appear to be regulated by QscR in transcriptome studies were not direct targets of QscR. Deletion of PA1897 recapitulates the early QS activation phenotype of a QscR-null mutant, and the phenotype of a QscR-null mutant was complemented by PA1895-1897 but not by PA1897 alone. We conclude that QscR acts to modulate quorum sensing through regulation of a single operon, apparently raising the QS threshold of the population and providing a “brake” on QS autoinduction. Quorum sensing, a cell-cell communication system, is broadly distributed among bacteria and is commonly used to regulate the production of shared products. An important consequence of quorum sensing is a delay in production of certain products until the population density is high. The bacterium Pseudomonas aeruginosa has a particularly complicated quorum sensing system involving multiple signals and receptors. One of these receptors, QscR, downregulates gene expression, unlike the other receptors in P. aeruginosa. QscR does so by inducing the expression of a single operon whose function provides an element of resistance to a population reaching a quorum. This finding has importance for design of quorum sensing inhibitory strategies and can also inform design of synthetic biological circuits that use quorum sensing receptors to regulate gene expression.