Counteractive Balancing of Transcriptome Expression Involving CodY and CovRS in Streptococcus pyogenes
Counteractive Balancing of Transcriptome Expression Involving CodY and CovRS in Streptococcus pyogenes
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DOI：
10.1128/jb.00061-11
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发表时间：
2011-08-01
影响因子：
3.2
通讯作者：
Malke, Horst
中科院分区：
文献类型：
--
作者：
Kreth, Jens;Chen, Zhiyun;Malke, Horst
化脓性链球菌（A组链球菌[GAS]）以导致转录组适应性调节的方式响应环境变化。本研究的目的是了解两个全局转录调控因子CodY和CovRS如何协调S.化脓来自表达微阵列数据和定量逆转录-PCR（qRT-PCR）的结果显示，全局调节子CodY控制约250个基因的表达，或菌株NZ 131基因组的约17%。此外，codY基因被证明是负性自调节的，其蛋白质直接结合到具有CodY结合位点的启动子区域。在进一步的研究中，使用C培养基在生长期依赖性条件下分析了codY、covRS和codY-covRS突变对基因表达的影响，据报道，C培养基模拟了与宿主GAS感染期间发现的营养丰富和饥饿条件相似的营养丰富和饥饿条件。几种毒力表型的其他生物学实验，包括菌毛蛋白产生，生物膜形成和NAD糖水解酶活性，证明了CodY和CovRS在其调节中的作用。总体数据的相关性分析显示，在指数生长的细胞中，CodY和CovRS以相反的方向起作用，CodY刺激和CovRS抑制核心基因组的大部分，包括许多毒力因子。这是全球转录调节因子的转录组表达的反作用平衡的第一份报告，并提供了重要的洞察GAS如何通过整合重要的细胞外和细胞内信息来调节基因表达。
Streptococcus pyogenes (group A streptococcus [GAS]) responds to environmental changes in a manner that results in an adaptive regulation of the transcriptome. The objective of the present study was to understand how two global transcriptional regulators, CodY and CovRS, coordinate the transcriptional network in S. pyogenes. Results from expression microarray data and quantitative reverse transcription-PCR (qRT-PCR) showed that the global regulator CodY controls the expression of about 250 genes, or about 17% of the genome of strain NZ131. Additionally, the codY gene was shown to be negatively autoregulated, with its protein binding directly to the promoter region with a CodY binding site. In further studies, the influence of codY, covRS, and codY-covRS mutations on gene expression was analyzed in growth phase-dependent conditions using C medium, reported to mimic nutritional abundance and famine conditions similar to those found during host GAS infection. Additional biological experiments of several virulence phenotypes, including pilin production, biofilm formation, and NAD glycohydrolase activity, demonstrated the role that both CodY and CovRS play in their regulation. Correlation analysis of the overall data revealed that, in exponentially growing cells, CodY and CovRS act in opposite directions, with CodY stimulating and CovRS repressing a substantial fraction of the core genome, including many virulence factors. This is the first report of counteractive balancing of transcriptome expression by global transcription regulators and provides important insight into how GAS modulates gene expression by integrating important extracellular and intracellular information.