Oligoribonuclease is required for the type III secretion system and pathogenesis of Pseudomonas aeruginosa
Oligoribonuclease is required for the type III secretion system and pathogenesis of Pseudomonas aeruginosa
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铜绿假单胞菌的 III 型分泌系统和发病机制需要寡糖核酸酶
DOI：
10.1016/j.micres.2016.05.002
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发表时间：
2016-01-01
影响因子：
6.7
通讯作者：
Cheng, Zhihui
中科院分区：
文献类型：
--
作者：
Chen, Gukui;Zhao, Qiang;Cheng, Zhihui
寡聚核糖核酸酶（Orn）是降解纳米RNA的3 '至5'外切核酸酶，其可充当在启动子的显著部分处的转录起始的引物。作为Orn的底物之一，pGpG抑制含有EAL结构域的磷酸二酯酶（PDE）的酶活性，从而增加细胞内环二GMP（c-di-GMP）水平。在这里，我们发现铜绿假单胞菌的orn突变体显示出降低的细胞毒性，这主要是由于缺乏III型分泌系统（T3SS）。鉴于T3SS在致病性中的重要性，我们检查了小鼠急性肺炎模型中的细菌毒力，发现与野生型PA14菌株相比，Delta orn突变体高度减毒。过表达的EAL结构域含有PDE降低了c-di-GMP水平，以及生物膜形成的三角洲突变体。然而，没有观察到对T3SS基因表达的影响，表明增加的c-di-GMP水平不是Delta orn突变体中T3SS缺陷的唯一原因。总之，我们的研究结果表明，Orn在表达T3SS以及铜绿假单胞菌的发病机制中起着重要作用。(C)2016 Elsevier GmbH. All rights reserved.
Oligoribonuclease (Orn) is a 3' to 5' exonuclease that degrades nanoRNAs, which can serve as primers for transcription initiation at a significant fraction of promoters. One of Orn's substrates, pGpG inhibits the enzymatic activity of EAL-domain containing phosphodiesterases (PDEs), thereby increasing intracellular cyclic-di-GMP (c-di-GMP) level. Here, we found that an orn mutant of Pseudomonas aeruginosa displayed reduced cytotoxicity, which was mainly due to deficient type III secretion system (T3SS). Given the importance of T3SS in pathogenicity, we examined the bacterial virulence in a mouse acute pneumonia model and found that the Delta orn mutant was highly attenuated compared to the wild type PA14 strain. Overexpression of an EAL domain-containing PDE reduced the c-di-GMP level as well as biofilm formation in the Delta orn mutant. However, no effect was observed on the expression of T3SS genes, suggesting that increased c-di-GMP level is not the solely cause of defective T3SS in the Delta orn mutant. Overall, our results demonstrated an essential role of Orn in the expression of T3SS as well as pathogenesis of P. aeruginosa. (C) 2016 Elsevier GmbH. All rights reserved.