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Revealing 29 sets of independently modulated genes in Staphylococcus aureus, their regulators, and role in key physiological response.
Proceedings of the National Academy of Sciences of the United States of America ( IF 11.1 ) Pub Date : 2020-07-21 , DOI: 10.1073/pnas.2008413117
Saugat Poudel 1 , Hannah Tsunemoto 2 , Yara Seif 1 , Anand V Sastry 1 , Richard Szubin 1 , Sibei Xu 1 , Henrique Machado 1 , Connor A Olson 1 , Amitesh Anand 1 , Joe Pogliano 2 , Victor Nizet 3, 4 , Bernhard O Palsson 3, 5
Affiliation  

The ability of Staphylococcus aureus to infect many different tissue sites is enabled, in part, by its transcriptional regulatory network (TRN) that coordinates its gene expression to respond to different environments. We elucidated the organization and activity of this TRN by applying independent component analysis to a compendium of 108 RNA-sequencing expression profiles from two S. aureus clinical strains (TCH1516 and LAC). ICA decomposed the S. aureus transcriptome into 29 independently modulated sets of genes (i-modulons) that revealed: 1) High confidence associations between 21 i-modulons and known regulators; 2) an association between an i-modulon and σS, whose regulatory role was previously undefined; 3) the regulatory organization of 65 virulence factors in the form of three i-modulons associated with AgrR, SaeR, and Vim-3; 4) the roles of three key transcription factors (CodY, Fur, and CcpA) in coordinating the metabolic and regulatory networks; and 5) a low-dimensional representation, involving the function of few transcription factors of changes in gene expression between two laboratory media (RPMI, cation adjust Mueller Hinton broth) and two physiological media (blood and serum). This representation of the TRN covers 842 genes representing 76% of the variance in gene expression that provides a quantitative reconstruction of transcriptional modules in S. aureus, and a platform enabling its full elucidation.



中文翻译:

揭示金黄色葡萄球菌中 29 组独立调节的基因、它们的调节因子以及在关键生理反应中的作用。

的能力,金黄色葡萄球菌感染多种不同组织部位被启用,部分地通过协调其基因表达不同的环境响应其转录调控网络(TRN)。我们通过将独立成分分析应用于来自两个金黄色葡萄球菌临床菌株(TCH1516 和 LAC)的 108 个 RNA 测序表达谱的概要,阐明了该 TRN 的组织和活性。ICA 分解金黄色葡萄球菌转录组转化为 29 组独立调节的基因(i-modulons),显示:1)21 个 i-modulons 与已知调节因子之间的高可信度关联;2) i-modulon 和 σS 之间的关联,其调节作用以前未定义;3) 以与 AgrR、SaeR 和 Vim-3 相关的三种 i-modulon 形式存在的 65 种毒力因子的调节组织;4) 三个关键转录因子(CodY、Fur 和 CcpA)在协调代谢和调节网络中的作用;和5)低维表示,涉及两种实验室培养基(RPMI,阳离子调节Mueller Hinton肉汤)和两种生理培养基(血液和血清)之间基因表达变化的少数转录因子的功能。金黄色葡萄球菌,以及一个能够对其进行全面阐明的平台。

更新日期:2020-07-22
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