The stringent response and physiological roles of (pp)pGpp in bacteria.

文献信息

DOI	10.1038/s41579-020-00470-y
PMID	33149273
期刊	Nature reviews. Microbiology
影响因子	103.3
JCR 分区	Q1
发表年份	2021
被引次数	194
关键词	严格反应, 警报核苷酸, 细菌致病性
文献类型	Journal Article, Research Support, Non-U.S. Gov't, Review
ISSN	1740-1526
页码	256-271
期号	19(4)
作者	Sophie E Irving, Naznin R Choudhury, Rebecca M Corrigan

一句话小结

本文综述了由ppGpp和pppGpp介导的严格反应信号系统，强调了这些警报分子在细菌应对营养缺乏时的复杂功能及其对RNA聚合酶和多条细胞通路的调控作用。研究表明，这些核苷酸不仅在细菌的生理过程中扮演重要角色，还与细菌的致病性及慢性感染调节密切相关，揭示了其在微生物学和医学中的重要意义。

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严格反应 · 警报核苷酸 · 细菌致病性

摘要

严格反应是一种由警报分子四磷酸鸟苷（ppGpp）和五磷酸鸟苷（pppGpp）介导的应激信号系统，响应营养缺乏。近期研究突出了这些警报分子的复杂性及其所控制的广泛功能。本综述更新了我们对参与ppGpp、pppGpp和鸟苷5'-单磷酸3'-二磷酸（pGpp）（统称为（pp)pGpp）代谢的酶的当前理解，包括那些已知可以生成pGpp及其类似物（pp)pApp的酶。我们描述了与RNA聚合酶的广泛相互作用，以及（pp)pGpp所控制的更广泛的细胞靶向通路，包括DNA复制、转录、核苷酸合成、核糖体生物合成与功能，以及脂质代谢。最后，我们回顾了ppGpp和pppGpp在细菌致病性中的作用，并提供了这些核苷酸在调节毒力和慢性感染多个方面的参与实例。

英文摘要

The stringent response is a stress signalling system mediated by the alarmones guanosine tetraphosphate (ppGpp) and guanosine pentaphosphate (pppGpp) in response to nutrient deprivation. Recent research highlights the complexity and broad range of functions that these alarmones control. This Review provides an update on our current understanding of the enzymes involved in ppGpp, pppGpp and guanosine 5'-monophosphate 3'-diphosphate (pGpp) (collectively (pp)pGpp) turnover, including those shown to produce pGpp and its analogue (pp)pApp. We describe the well-known interactions with RNA polymerase as well as a broader range of cellular target pathways controlled by (pp)pGpp, including DNA replication, transcription, nucleotide synthesis, ribosome biogenesis and function, as well as lipid metabolism. Finally, we review the role of ppGpp and pppGpp in bacterial pathogenesis, providing examples of how these nucleotides are involved in regulating many aspects of virulence and chronic infection.

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主要研究问题

核心洞察

1. 研究背景和目的

该研究聚焦于细菌中的严格反应机制，这是一种由营养缺乏引发的应激信号系统。研究的核心是两种重要的信号分子：鸟苷酸四磷酸（ppGpp）和鸟苷酸五磷酸（pppGpp），统称为（pp)pGpp。这些报警分子在细菌应对营养缺乏时发挥关键作用。研究的目的在于深入了解（pp)pGpp的代谢酶、其在细菌生理中的多重功能，以及其在细菌致病性中的作用。

2. 主要方法和发现

本综述整合了当前关于（pp)pGpp的代谢酶的研究，包括能生成pGpp及其类似物（pp)pApp的酶。此外，研究还探讨了（pp)pGpp与RNA聚合酶的已知相互作用，以及这些警报分子对多个细胞途径的调控，涵盖了DNA复制、转录、核苷酸合成、核糖体生物合成和功能、以及脂质代谢等方面。研究还提供了（pp)pGpp在细菌致病机制中的角色示例，说明这些核苷酸如何调节细菌的毒力和慢性感染。

3. 核心结论

研究表明，（pp)pGpp不仅在应对环境压力方面起着至关重要的作用，还通过调节多条重要生理通路，影响细菌生长和致病性。特别是在营养缺乏的情况下，这些警报分子能够协调细菌的生理反应，确保细胞的存活和适应性。此外，ppGpp和pppGpp在细菌的毒力和感染过程中的作用提示了它们在病原体生物学上的重要性。

4. 研究意义和影响

本研究对理解细菌如何在不利环境中生存和适应具有重要意义。通过揭示（pp)pGpp的多重生理角色和调控机制，能够为开发新型抗菌策略提供理论基础。鉴于这些信号分子在细菌致病性中的关键作用，针对（pp)pGpp的干预可能成为一种新的抗感染策略，为控制细菌感染提供新的思路和方法。这项研究不仅丰富了我们对细菌应激反应的理解，也为未来的临床应用和药物开发奠定了基础。

参考文献

Bacterial lifestyle shapes stringent response activation. - Cara C Boutte;Sean Crosson - Trends in microbiology (2013)
(p)ppGpp: still magical? - Katarzyna Potrykus;Michael Cashel - Annual review of microbiology (2008)
The RelA/SpoT homolog (RSH) superfamily: distribution and functional evolution of ppGpp synthetases and hydrolases across the tree of life. - Gemma C Atkinson;Tanel Tenson;Vasili Hauryliuk - PloS one (2011)
From (p)ppGpp to (pp)pGpp: Characterization of Regulatory Effects of pGpp Synthesized by the Small Alarmone Synthetase of Enterococcus faecalis. - Anthony O Gaca;Pavel Kudrin;Cristina Colomer-Winter;Jelena Beljantseva;Kuanqing Liu;Brent Anderson;Jue D Wang;Dominik Rejman;Katarzyna Potrykus;Michael Cashel;Vasili Hauryliuk;José A Lemos - Journal of bacteriology (2015)
The Ps and Qs of alarmone synthesis in Staphylococcus aureus. - Ning Yang;Shujie Xie;Nga-Yeung Tang;Mei Yee Choi;Ying Wang;Rory M Watt - PloS one (2019)
Identification and Functional Characterization of Small Alarmone Synthetases in Corynebacterium glutamicum. - Matthias Ruwe;Jörn Kalinowski;Marcus Persicke - Frontiers in microbiology (2017)
Infection and chronic disease activate a brain-muscle signaling axis that regulates muscle performance. - Shuo Yang;Meijie Tian;Yulong Dai;Shengyong Feng;Yunyun Wang;Deepak Chhangani;Tiffany Ou;Wenle Li;Ze Yang;Jennifer McAdow;Diego E Rincon-Limas;Xin Yin;Wanbo Tai;Gong Cheng;Aaron Johnson - bioRxiv : the preprint server for biology (2022)
Make and break the alarmone: regulation of (p)ppGpp synthetase/hydrolase enzymes in bacteria. - Séverin Ronneau;Régis Hallez - FEMS microbiology reviews (2019)
Triggering the stringent response: signals responsible for activating (p)ppGpp synthesis in bacteria. - Sophie E Irving;Rebecca M Corrigan - Microbiology (Reading, England) (2018)
Two compounds implicated in the function of the RC gene of Escherichia coli. - M Cashel;J Gallant - Nature (1969)

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... (184 更多篇文献)

The stringent response and physiological roles of (pp)pGpp in bacteria. ​

文献信息 ​

一句话小结 ​

在麦伴科研 (maltsci.com) 搜索更多文献 ​

摘要 ​

英文摘要 ​

麦伴智能科研服务 ​

主要研究问题 ​

核心洞察 ​

1. 研究背景和目的 ​

2. 主要方法和发现 ​

3. 核心结论 ​

4. 研究意义和影响 ​

参考文献 ​

引用本文的文献 ​