Nitrosative stress in enterobacteria - the S-nitrosoproteome and an assessment of cellular protective functions in vitro and in vivo

肠细菌中的亚硝化应激 - S-亚硝基蛋白质组以及体外和体内细胞保护功能的评估

• 批准号: BB/E015883/1
• 负责人: Robert K Poole
• 金额: $ 45.07万
• 依托单位: University of Sheffield
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FE015883%2F1
• 关键词: Nitrosative; stress; enterobacteria; nitrosoproteome; assessment

Molecules that are important in biology include not only familiar organic macromolecules (nucleic acids, proteins, fats, carbohydrates) but also small inorganic molecules or ions. One of the most important of these, and the most topical, is nitrogen monoxide (nitric oxide, NO). This gas is produced by animals, plants and microbes and is also generated chemically in many environments. NO is potentially toxic to microbes, which must defend themselves from its chemical reactivity. The current interest in NO by research scientists arises from the fact that it is an important signaling molecule in animals and plants, involved in controlling blood vessel relaxation, nerve function and immunity. In addition, NO reacts with macromolecules, modifying their function with important biological implications. These processes (called nitrosation, nitrosylation, nitration), in which the NO group is covalently bound to the macromolecule, are highly selective and so we cannot predict which proteins will be modified. This research project sets out to measure the extent of these reactions inside intact bacteria. We wish also to test the idea that the defences used by bacteria against NO and related chemicals lead to a reduction in protein modification by NO. Finally, we wish to see whether bacteria that have been engulfed by white blood cells are prone to these modifications and whether the bacterial defence mechanisms limit these reactions. Overall, these experiments will help us to understand which molecules within bacteria are susceptible to NO attack and whether Man's antimicrobial strategies might benefit from this knowledge.

生物学中重要的分子不仅包括常见的有机大分子（核酸、蛋白质、脂肪、碳水化合物），还包括无机小分子或离子。其中最重要的，也是最热门的，是一氧化氮（一氧化氮，NO）。这种气体是由动物、植物和微生物产生的，在许多环境中也是化学产生的。NO对微生物具有潜在的毒性，微生物必须保护自己免受其化学反应的影响。研究科学家目前对NO的兴趣源于它是动物和植物中重要的信号分子，参与控制血管舒张，神经功能和免疫力。此外，NO与大分子反应，改变它们的功能，具有重要的生物学意义。这些过程（称为亚硝化，亚硝基化，硝化），其中NO基团与大分子共价结合，具有高度选择性，因此我们无法预测哪些蛋白质将被修饰。该研究项目旨在测量完整细菌内这些反应的程度。我们还希望测试细菌对NO和相关化学物质的防御导致NO对蛋白质修饰减少的想法。最后，我们希望了解被白色血细胞吞噬的细菌是否易于进行这些修饰，以及细菌防御机制是否限制了这些反应。总的来说，这些实验将帮助我们了解细菌内的哪些分子容易受到NO的攻击，以及人类的抗菌策略是否会从这些知识中受益。

项目成果

KatG from Salmonella typhimurium is a peroxynitritase.

来自鼠伤寒沙门氏菌的 KatG 是一种过氧亚硝酸酶。

• DOI: 10.1016/j.febslet.2010.03.029
• 发表时间: 2010
• 期刊: FEBS letters
• 影响因子: 3.5
• 作者: McLean S

Globins and other nitric oxide-reactive proteins. Preface.

球蛋白和其他一氧化氮反应蛋白。

• DOI: 10.1016/s0076-6879(07)37033-x
• 发表时间: 2008
• 期刊: Methods in enzymology
• 作者: Poole RK

Bacterial nitric oxide detoxification prevents host cell S-nitrosothiol formation: a novel mechanism of bacterial pathogenesis.

• DOI: 10.1096/fj.08-128330
• 发表时间: 2010-01
• 期刊: FASEB journal : official publication of the Federation of American Societies for Experimental Biology
• 作者: Laver JR;Stevanin TM;Messenger SL;Lunn AD;Lee ME;Moir JW;Poole RK;Read RC
• 通讯作者: Read RC

The cytochrome bd-I respiratory oxidase augments survival of multidrug-resistant Escherichia coli during infection.

• DOI: 10.1038/srep35285
• 发表时间: 2016-10-21
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Shepherd M;Achard ME;Idris A;Totsika M;Phan MD;Peters KM;Sarkar S;Ribeiro CA;Holyoake LV;Ladakis D;Ulett GC;Sweet MJ;Poole RK;McEwan AG;Schembri MA
• 通讯作者: Schembri MA

Nitrosothiols in bacterial pathogens and pathogenesis.

• DOI: 10.1089/ars.2012.4767
• 发表时间: 2013-01
• 期刊: Antioxidants & redox signaling
• 影响因子: 6.6
• 作者: Jay R. Laver;Samantha McLean;Lesley A. H. Bowman;L. Harrison;R. Read;R. Poole