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对γ-破坏菌株和亲本野生型菌株氧化应激的全球转录组反应的比较分析。

Comparative Analysis of the Global Transcriptomic Response to Oxidative Stress of -Disrupted and Parental Wild Type Strains.

作者信息

Zaide Galia, Elia Uri, Cohen-Gihon Inbar, Israeli Ma'ayan, Rotem Shahar, Israeli Ofir, Ehrlich Sharon, Cohen Hila, Lazar Shirley, Beth-Din Adi, Shafferman Avigdor, Zvi Anat, Cohen Ofer, Chitlaru Theodor

机构信息

Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona 74100, Israel.

出版信息

Microorganisms. 2020 Nov 30;8(12):1896. doi: 10.3390/microorganisms8121896.

Abstract

We previously demonstrated that the HtrA (High Temperature Requirement A) protease/chaperone active in the quality control of protein synthesis, represents an important virulence determinant of . Virulence attenuation of -disrupted strains was attributed to susceptibility of Δ strains to stress insults, as evidenced by affected growth under various stress conditions. Here, we report a comparative RNA-seq transcriptomic study generating a database of differentially expressed genes in the -disrupted and wild type parental strains under oxidative stress. The study demonstrates that, apart from protease and chaperone activities, HtrA exerts a regulatory role influencing expression of more than 1000 genes under stress. Functional analysis of groups or individual genes exhibiting strain-specific modulation, evidenced (i) massive downregulation in the Δ and upregulation in the WT strains of various transcriptional regulators, (ii) downregulation of translation processes in the WT strain, and (iii) downregulation of metal ion binding functions and upregulation of sporulation-associated functions in the Δ strain. These modulated functions are extensively discussed. Fifteen genes uniquely upregulated in the wild type strain were further interrogated for their modulation in response to other stress regimens. Overexpression of one of these genes, encoding for MazG (a nucleoside triphosphate pyrophosphohydrolase involved in various stress responses in other bacteria), in the Δ strain resulted in partial alleviation of the HO-sensitive phenotype.

摘要

我们先前证明,在蛋白质合成质量控制中具有活性的HtrA(高温需求A)蛋白酶/伴侣蛋白是……的重要毒力决定因素。缺失HtrA的菌株毒力减弱归因于Δ菌株对压力损伤的敏感性,这在各种压力条件下受影响的生长中得到证明。在此,我们报告了一项比较RNA测序转录组学研究,该研究生成了在氧化应激下缺失HtrA和野生型亲本菌株中差异表达基因的数据库。该研究表明,除了蛋白酶和伴侣蛋白活性外,HtrA在压力下还发挥调节作用,影响1000多个基因的表达。对表现出菌株特异性调节的基因群或单个基因的功能分析表明:(i)在Δ菌株中各种转录调节因子大量下调,而在野生型菌株中上调;(ii)野生型菌株中翻译过程下调;(iii)Δ菌株中金属离子结合功能下调,孢子形成相关功能上调。对这些调节功能进行了广泛讨论。对野生型菌株中独特上调的15个基因进一步研究了它们对其他应激方案的调节情况。在Δ菌株中过表达其中一个基因,该基因编码MazG(一种参与其他细菌各种应激反应的核苷三磷酸焦磷酸水解酶),导致对HO敏感表型部分缓解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c64/7760947/7030e41d51f6/microorganisms-08-01896-g001.jpg

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