H(2)O(2) concentration-dependent kinetics of gene expression: linking the intensity of oxidative stress and mycobacterial physiological adaptation.
H(2)O(2) concentration-dependent kinetics of gene expression: linking the intensity of oxidative stress and mycobacterial physiological adaptation.
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DOI：
10.1080/22221751.2022.2034484
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发表时间：
2022-12
影响因子：
13.2
通讯作者：
Lyu LD
中科院分区：
文献类型：
--
作者：
Wu M;Shan W;Zhao GP;Lyu LD
对氧化应激的防御对结核分枝杆菌在巨噬细胞内生存和复制至关重要。分枝杆菌已经进化出多层抗氧化系统，包括清除酶、铁稳态、修复途径和代谢适应，以应对氧化应激。然而，这些系统如何协调以使其能够对不同强度的氧化应激进行生理适应仍不清楚。为了解决这一问题，我们以污垢分枝杆菌为模型，研究了在抑菌浓度从1 mM到10 mM的范围内，具有良好特性的抗氧化基因的表达动力学。我们的结果表明，所选择的大多数基因都以过氧化氢浓度依赖的方式表达，但有一部分亚群表现出持续的诱导或抑制，没有剂量效应，反映了过氧化氢浓度依赖的生理适应。通过对协调基因表达的动态分析，我们证明了过氧化氢清除酶、DNA损伤反应和Fe-S簇修复功能的表达与氧化胁迫的强度显著相关。对mbtB、IRTA和dna E2的持续诱导表明，分枝杆菌可能会将增加的铁获取和容易出错的病变旁路功能作为对抗氧化损伤的基本策略，这与大肠杆菌的防御策略不同，其特征是缩小铁库和延缓DNA修复。此外，三羧酸循环、乙醛分流循环和柠檬酸甲酯循环之间不同的基因表达动力学表明，分枝杆菌可以根据氧化应激的强度动态地重新定向其代谢流。这项工作定义了依赖于过氧化氢浓度的基因表达动力学，并为分枝杆菌的抗氧化防御策略提供了独特的见解。
Defence against oxidative stress is crucial for Mycobacterium tuberculosis to survive and replicate within macrophages. Mycobacteria have evolved multilayer antioxidant systems, including scavenging enzymes, iron homeostasis, repair pathways, and metabolic adaptation, for coping with oxidative stress. How these systems are coordinated to enable the physiological adaptation to different intensities of oxidative stress, however, remains unclear. To address this, we investigated the expression kinetics of the well-characterized antioxidant genes at bacteriostatic H2O2 concentrations ranging from 1 mM to 10 mM employing Mycolicibacterium smegmatis as a model. Our results showed that most of the selected genes were expressed in a H2O2 concentration-dependent manner, whereas a subset exhibited sustained induction or repression without dose–effect, reflecting H2O2 concentration-dependent physiological adaptations. Through analyzing the dynamics of the coordinated gene expression, we demonstrated that the expressions of the H2O2 scavenging enzymes, DNA damage response, and Fe–S cluster repair function were strikingly correlated to the intensity of oxidative stress. The sustained induction of mbtB, irtA, and dnaE2 indicated that mycobacteria might deploy increased iron acquisition and error-prone lesion bypass function as fundamental strategies to counteract oxidative damages, which are distinct from the defence tactics of Escherichia coli characterized by shrinking the iron pool and delaying the DNA repair. Moreover, the distinct gene expression kinetics among the tricarboxylic acid cycle, glyoxylate shunt, and methylcitrate cycle suggested that mycobacteria could dynamically redirect its metabolic fluxes according to the intensity of oxidative stress. This work defines the H2O2 concentration-dependent gene expression kinetics and provides unique insights into mycobacterial antioxidant defence strategies.
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DOI：
10.1038/s41579-018-0013-4
发表时间：
2018-08
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
Ehrt S;Schnappinger D;Rhee KY
通讯作者：
Rhee KY
影响因子：
64.5
作者：
Boshoff, HIM;Reed, MB;Mizrahi, V
通讯作者：
Mizrahi, V
影响因子：
3.6
作者：
Dussurget, O;Rodriguez, M;Smith, I
通讯作者：
Smith, I
DOI：
10.1073/pnas.0707723105
发表时间：
2008-06-17
影响因子：
11.1
作者：
Leichert, Lars I.;Gehrke, Florian;Jakob, Ursula
通讯作者：
Jakob, Ursula
影响因子：
3.2
作者：
IMLAY, JA;LINN, S
通讯作者：
LINN, S