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Use of Molecular Hydrogen by Salmonella typhimurium

鼠伤寒沙门氏菌对分子氢的利用

基本信息

批准号：
7849924
负责人：
ROBERT J. MAIER
金额：
$ 22.28万
依托单位：
UNIVERSITY OF GEORGIA
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-06-01 至 2012-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7849924
关键词：
Address Affect Affinity Amino Acids Animals Area Azotobacter Bacteria Binding Biochemical Biology Bradyrhizobium Carbon Categories Cations Cells Chelating Agents Communicable Diseases Communities Cytochrome a Cytochromes Development Disease Educational process of instructing Electrons Enteral Enterobacteriaceae Environment Enzymes Food Funding Goals Grant Growth Helicobacter Helicobacter hepaticus Human Hydrogen Hydrogenase Individual Infection Knowledge Light Measurement Measures Mediating Membrane Metals Molecular National Institute of Allergy and Infectious Disease Nickel Outcome Oxygen Parents Physiological Predisposition Procedures Process Property Proteins Research Respiration Respiratory Chain Role Salmonella Salmonella typhimurium Science Scientist Site Source Starvation System Water Supply Work biodefense chelation cofactor combat design enteric pathogen expectation mutant novel strategies oxidation particle pathogen prevent research study respiratory respiratory protein response therapeutic development uptake

项目摘要

DESCRIPTION (provided by applicant): This proposal is designed to further our knowledge of the respiratory use of molecular hydrogen by Salmonella typhimurium. The long-term outcome of these exploratory studies is to assess the feasibility of targeting this process via metal chelation in order to prevent enteric bacterial-mediated diseases. Infection by the enteric human pathogen Salmonella typhimurium result in millions of cases of diarrheal illness annually and the prospect of the malevolent introduction of enteric pathogens into food or water supplies makes them an NIAID category B biodefense priority concern. The pathogen has excellent capacity to split molecular H2 and use the low potential electrons in a respiratory manner (with O2 as the terminal acceptor). It is proposed to identify the respiratory proteins used by the pathogen to metabolize molecular hydrogen. Characterizations of the role of H2 oxidation will be approached by comparing mutant strains in each of the hydrogenases for H2 affinities associated with each H2-binding enzyme, for their individual ability to facilitate amino acid transport, and to reduce a cytochrome-containing respiratory chain. The affects of nickel chelators (i.e. nickel starvation conditions) on the expression of each individual hydrogenase will be assessed by studying the mutant strains. The major research areas covered by this proposal include both pathogen biology and exploratory therapeutics development to combat infectious disease. Salmonella bacteria result in millions of cases of human diarrheal disease annually. Inhibiting growth of the bacterium within animal hosts is the long-term goal of this work.

描述（由申请人提供）：本提案旨在进一步了解鼠伤寒沙门菌对分子氢的呼吸利用。这些探索性研究的长期结果是评估通过金属螯合靶向这一过程以预防肠道细菌介导疾病的可行性。人类肠道致病菌鼠伤寒沙门氏菌的感染每年导致数百万例腹泻病例，肠道致病菌恶意引入食物或供水的前景使其成为NIAID B类生物防御重点关注的问题。病原体具有极好的分裂H2分子的能力，并以呼吸方式利用低电位电子（以O2为终端受体）。建议鉴定病原体用于代谢分子氢的呼吸蛋白。通过比较每种氢化酶的突变菌株，H2与每种H2结合酶的亲和关系，以及它们促进氨基酸运输和减少含有细胞色素的呼吸链的个体能力，我们将探讨H2氧化作用的特征。镍螯合剂（即镍饥饿条件）对每种氢化酶表达的影响将通过研究突变菌株来评估。本建议涵盖的主要研究领域包括病原体生物学和探索治疗发展，以对抗传染病。