The Pyocin Regulator PrtR Regulates Virulence Expression of Pseudomonas aeruginosa by Modulation of Gac/Rsm System and c-di-GMP Signaling Pathway
The Pyocin Regulator PrtR Regulates Virulence Expression of Pseudomonas aeruginosa by Modulation of Gac/Rsm System and c-di-GMP Signaling Pathway
复制标题
Pyocin 调节剂 PrtR 通过调节 Gac/Rsm 系统和 c-di-GMP 信号通路来调节铜绿假单胞菌的毒力表达。
DOI：
10.1128/iai.00602-20
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发表时间：
2021-02-01
影响因子：
3.1
通讯作者：
Whiteley, Marvin
中科院分区：
文献类型：
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作者：
Jiao, Hongying;Li, Fan;Whiteley, Marvin
在铜绿假单胞菌中，第二信使环二GMP和Gac/Rsm信号通路与从急性到慢性感染的转变相关。因此，确定细菌中控制生活方式选择的分子机制非常重要。在这里，我们确定了一种新的环状二GMP调节剂，PrtR，它被证明可以通过抑制PrtN抑制绿脓菌素的产生，并通过PtrB激活III型分泌系统（T3 SS）。与野生型菌株或prtN突变体相比，prtR prtN双突变体表现出一个克隆和超生物膜表型，以及细胞内c-di-GMP水平的增加。有趣的是，二鸟苷酸环化酶（DGC）基因，siaD，被PrtR抑制。进一步的实验表明，PrtR直接与SiaD相互作用，促进c-di-GMP在细胞中的积累。我们还证明了PrtR调节Gac/Rsm系统的活性，从而影响T3 SS和VI型分泌系统（T6 SS）的表达和生物膜的形成。综上所述，本研究结果表明，PrtR作为c-di-GMP调节剂，在铜绿假单胞菌适应机会性感染中起关键作用。此外，这项研究揭示了一种新的机制PrtR介导的调节生活方式的转变，通过Gac/RSM和c-di-GMP信号网络。
In Pseudomonas aeruginosa, the second messenger cyclic-di-GMP and Gac/Rsm signaling pathways are associated with the transition from acute to chronic infection. Therefore, identification of the molecular mechanisms that govern lifestyle choice in bacteria is very important. Here, we identified a novel cyclic-di-GMP modulator, PrtR, which was shown to repress pyocin production by inhibition of PrtN and activate the type III secretion system (T3SS) through PtrB. Compared to a wild-type strain or a prtN mutant, the prtR prtN double mutant exhibited a wrinkly colony and hyperbiofilm phenotype, as well as an increase in intracellular c-di-GMP levels. Interestingly, a diguanylate cyclase (DGC) gene, siaD, was repressed by PrtR. Further experiments revealed that PrtR directly interacts with SiaD and facilitates the accumulation of c-di-GMP in cells. We also demonstrated that PrtR regulates the activity of the Gac/Rsm system, thus affecting expression of the T3SS and type VI secretion system (T6SS) and the formation of biofilm. Taken together, the present findings indicate that PrtR, as a c-di-GMP modulator, plays key roles in the adaptation to opportunistic infection of P. aeruginosa. Additionally, this study revealed a novel mechanism for PrtR-mediated regulation of the lifestyle transition via the Gac/Rsm and c-di-GMP signaling networks.