The global regulator Crc orchestrates the metabolic robustness underlying oxidative stress resistance in Pseudomonas aeruginosa
The global regulator Crc orchestrates the metabolic robustness underlying oxidative stress resistance in Pseudomonas aeruginosa
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DOI：
10.1111/1462-2920.14471
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发表时间：
2019-03-01
影响因子：
5.1
通讯作者：
Nikel, Pablo, I
中科院分区：
文献类型：
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作者：
Corona, Fernando;Luis Martinez, Jose;Nikel, Pablo, I
假单胞菌属细菌的显著代谢多样性使它们能够在非常不同的环境条件下存活。铜绿假单胞菌，最相关的机会致病菌之一，是这种适应性的一个很好的例子。调节这些代谢和生理特征的调节网络之间的相互作用才刚刚开始被详细探索。由Crc蛋白控制的碳分解代谢物抑制控制参与次级碳源同化的几种酶和转运蛋白的可用性。然而，Crc对铜绿假单胞菌氧化还原代谢的调节作用（因此，对整体生理学的调节作用）迄今尚未被探索。在这项研究中，我们解决了铜绿假单胞菌PAO1的碳分解代谢物阻遏和代谢稳健性之间的密切联系。特别是，我们探讨了氧化应激，在中央碳代谢和细胞氧化还原状态的代谢重排之间的相互作用。通过采用定量生理学实验，多组学分析，关键基因的转录模式，体外代谢活性的测量和野生型菌株和同基因Delta crc衍生物中氧化还原平衡的直接定量的组合，我们证明Crc通过重塑该细菌中的核心代谢结构来协调铜绿假单胞菌对氧化应激的整体反应。
The remarkable metabolic versatility of bacteria of the genus Pseudomonas enable their survival across very diverse environmental conditions. P. aeruginosa, one of the most relevant opportunistic pathogens, is a prime example of this adaptability. The interplay between regulatory networks that mediate these metabolic and physiological features is just starting to be explored in detail. Carbon catabolite repression, governed by the Crc protein, controls the availability of several enzymes and transporters involved in the assimilation of secondary carbon sources. Yet, the regulation exerted by Crc on redox metabolism of P. aeruginosa (hence, on the overall physiology) had hitherto been unexplored. In this study, we address the intimate connection between carbon catabolite repression and metabolic robustness of P. aeruginosa PAO1. In particular, we explored the interplay between oxidative stress, metabolic rearrangements in central carbon metabolism and the cellular redox state. By adopting a combination of quantitative physiology experiments, multiomic analyses, transcriptional patterns of key genes, measurement of metabolic activities in vitro and direct quantification of redox balances both in the wild-type strain and in an isogenic Delta crc derivative, we demonstrate that Crc orchestrates the overall response of P. aeruginosa to oxidative stress via reshaping of the core metabolic architecture in this bacterium.