Use of Molecular Hydrogen by Salmonella typhimurium

描述（由申请方提供）：本提案旨在进一步了解鼠伤寒沙门氏菌对分子氢的呼吸使用。这些探索性研究的长期结果是评估通过金属螯合靶向该过程以预防肠道细菌介导的疾病的可行性。人类肠道病原体鼠伤寒沙门氏菌的感染每年导致数百万例腹泻病，并且肠道病原体恶意引入食物或水源的前景使其成为NIAID类别B生物防御优先关注的问题。该病原体具有良好的能力，分裂分子H2和使用低电位电子在呼吸的方式（与O2作为终端受体）。建议鉴定病原体用于代谢分子氢的呼吸蛋白。H2氧化的作用的表征将接近通过比较突变株在每个氢化酶的H2亲和力与每个H2结合酶，其个人的能力，以促进氨基酸运输，并减少含细胞色素的呼吸链。将通过研究突变菌株来评估镍螯合剂（即镍饥饿条件）对每种氢化酶表达的影响。这项建议涵盖的主要研究领域包括病原体生物学和探索性治疗方法的发展，以对抗传染病。 沙门氏菌每年导致数百万例人类腹泻病。抑制细菌在动物宿主体内的生长是这项工作的长期目标。

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.