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The Physiology of Oxidative Stress in Escherichia coli

大肠杆菌氧化应激的生理学

基本信息

批准号：
8686869
负责人：
JAMES A. IMLAY
金额：
$ 54.48万
依托单位：
UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
依托单位国家：
美国
项目类别：
财政年份：
1994
资助国家：
美国
起止时间：
1994-05-01 至 2017-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8686869
关键词：
Address Aerobic Aerobic Bacteria Amino Acids Anaerobic Bacteria Anaerobiosis Animal Model Antibiotic Therapy Antibiotics Autoimmune Diseases Bacteroides thetaiotaomicron Biochemistry Biological Biological Markers Bolus Infusion Cell Membrane Permeability Cells Cellular Stress Charge Chemicals Commit Complex Data Dose Effectiveness Electrons Environment Enzymatic Biochemistry Enzymes Escherichia coli Eukaryota Extravasation Gene Expression Profile Genes Growth Heme Hydro-Lyases Hydrogen Peroxide Immune response In Vitro Infection Injury Instruction Iron Knowledge Location Manganese Measurement Medical Metabolic Metals Methods Modeling Molecular Mononuclear Organism Oxidants Oxidases Oxidation-Reduction Oxidative Stress Oxygen Pathogenicity Pathway interactions Peptides Peroxidases Phagocytes Phenotype Physiologic pulse Physiological Physiology Process Production RNA Sequences Radiation Reactive Oxygen Species Ribosomes Role Stress Superoxides System Testing Toxic effect Weaning Work Yeasts base carcinogenesis catalase cell injury cell type chemotherapy coping experience feeding ferrochelatase genetic analysis inhibitor/antagonist interest isopropylmalate isomerase lactic acid bacteria metalloenzyme microbial mutant peptide deformylase periplasm protoporphyrin IX research study respiratory response theories trafficking

项目摘要

We seek to understand the impact that oxidative stress has upon organisms by addressing three overarching questions: How are reactive oxygen species formed in biological environments? What biomolecules do they damage? And how do cells defend themselves against them? We have employed E. coli as a model organism, in part because we have such a detailed understanding of its physiology and biochemistry, and in part because this facultative anaerobe can be genetically manipulated in the absence of oxygen. Our next set of specific aims addresses each of these three issues: 1. Are cytoplasmic enzymes shielded from H202 that is generated by periplasmic enzymes? Is intracellular formation of reactive oxygen species especially rapid inside aerated anaerobes? Are these species the primary factor in blocking their aerobic growth? Do antibiotics actually trigger H202 stress? 2. Does superoxide damage mononuclear iron enzymes ? Do oxidants inhibit ferrochelatase? What other targets of these oxidants can we discover through transcriptome analysis? 3. How completely can manganese-fed E. coli dispense with iron? How efficiently is manganese delivered to metalloenzymes? Do lactic-acid bacteria that routinely experience H202 stress employ manganese, rather than iron, in mononuclear non-redox enzymes? What about obligate aerobes, such as eukaryotes? These questions follow directly from the results of the current project. They are fundamental to our understanding of oxidative stress in contexts of medical interest, including the pathogenicity of obligate anaerobes, the effectiveness of antibiotic and antitumor treatments, and the mechanisms by which phagocytes suppress microbial infections.

我们试图了解氧化应激对生物体的影响，通过解决三个至关重要的问题，问题：活性氧是如何在生物环境中形成的？它们是什么生物分子损坏？细胞如何保护自己不受它们的侵害？我们使用了E。大肠杆菌作为模型生物，部分原因是我们对它的生理学和生物化学有如此详细的了解，部分原因是这种兼性厌氧菌可以在缺氧的情况下进行基因操作。我们的下一套具体目标针对这三个问题中的每一个： 1.细胞质酶是否可以免受周质酶产生的H202的影响？是细胞内活性氧的形成在有氧厌氧菌中特别迅速？这些物种是阻碍其有氧生长的主要因素？抗生素真的会引发H202应激吗？ 2.超氧化物损伤单核铁酶吗？氧化剂抑制亚铁螯合酶吗？什么其他我们可以通过转录组分析发现这些氧化剂的靶点吗？ 3.喂锰的E.大肠杆菌不含铁？锰的输送效率如何到金属酶经常经历H2O2应激的乳酸菌是否利用锰，而不是铁，在单核非氧化还原酶？那么专性需氧生物，如真核生物呢？这些问题直接来自当前项目的结果。他们是我们的基础，理解氧化应激在医学上的意义，包括致病性厌氧菌，抗生素和抗肿瘤治疗的有效性，以及吞噬细胞抑制微生物感染。