How Microbes Defend Themselves From Incoming Hydrogen Peroxide.

How Microbes Defend Themselves From Incoming Hydrogen Peroxide.
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DOI:
10.3389/fimmu.2021.667343
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发表时间:
2021
影响因子:
7.3
通讯作者:
Imlay JA
Imlay JA
中科院分区:
医学2区
文献类型:
--
作者:
Sen A;Imlay JA

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微生物在其中心代谢过程中依赖铁作为许多酶的辅助因子。活性氧(ROS)超氧化物和过氧化氢与铁迅速反应,在细胞内它们可以产生酶和DNA损伤。活性氧是在一些细菌栖息地通过非生物过程形成的。细菌对活性氧的脆弱性显然也被产生活性氧的宿主防御系统和细菌竞争对手利用。吞噬细胞衍生的可通过破坏细胞表面未识别的生物分子而使捕获的细菌中毒;目前尚不清楚吞噬H2O2是否也起到抑制细菌侵袭的作用,H2O2可以渗透到细胞内部。病原微生物和自由微生物都激活防御策略来保护自己免受H2O2的侵害。大多数细菌通过OxyR或PerR转录因子感知H2O2,而酵母则使用Grx3/Yap1系统。一般来说,这些调节剂诱导酶降低细胞质H2O2浓度,减少细胞内铁池,并修复H2O2介导的损伤。然而,个体生物已经定制了这些转录因子和它们的规则来适应它们特定的环境生态位。有些细菌甚至同时含有OxyR和PerR,这就提出了为什么它们需要这两个系统的问题。在实验室实验中,这些调节因子也可以对一氧化氮和二硫化物应激作出反应,尽管尚不清楚这些反应是否与生理相关。下一步是将这些研究扩展到自然环境中,这样我们就能更好地理解这些系统运作的环境。特别是,探索它们在微生物病原体感染宿主中可能发挥的作用是重要的。
Microbes rely upon iron as a cofactor for many enzymes in their central metabolic processes. The reactive oxygen species (ROS) superoxide and hydrogen peroxide react rapidly with iron, and inside cells they can generate both enzyme and DNA damage. ROS are formed in some bacterial habitats by abiotic processes. The vulnerability of bacteria to ROS is also apparently exploited by ROS-generating host defense systems and bacterial competitors. Phagocyte-derived can toxify captured bacteria by damaging unidentified biomolecules on the cell surface; it is unclear whether phagocytic H2O2, which can penetrate into the cell interior, also plays a role in suppressing bacterial invasion. Both pathogenic and free-living microbes activate defensive strategies to defend themselves against incoming H2O2. Most bacteria sense the H2O2 via OxyR or PerR transcription factors, whereas yeast uses the Grx3/Yap1 system. In general these regulators induce enzymes that reduce cytoplasmic H2O2 concentrations, decrease the intracellular iron pools, and repair the H2O2-mediated damage. However, individual organisms have tailored these transcription factors and their regulons to suit their particular environmental niches. Some bacteria even contain both OxyR and PerR, raising the question as to why they need both systems. In lab experiments these regulators can also respond to nitric oxide and disulfide stress, although it is unclear whether the responses are physiologically relevant. The next step is to extend these studies to natural environments, so that we can better understand the circumstances in which these systems act. In particular, it is important to probe the role they may play in enabling host infection by microbial pathogens.
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