Sodium bioenergetics in Yersinia pestis

鼠疫耶尔森氏菌的钠生物能学

• 批准号: 7828039
• 负责人: Claudia C Hase
• 金额: $ 21.93万
• 依托单位: OREGON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-07 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7828039
• 关键词: ATP Synthesis Pathway; Animal Model; Animals; Bacteria; Bacterial Genome; Bacterial Infections; Bioenergetics; Biological; Biological Assay; Blood Circulation; Cells; Chromosomes; Communicable Diseases; Communities; Complement; Complex; Coupling; Data; Development; Devices; Drug Delivery Systems; Ecology; Energy Metabolism; Environment; Enzymes; Flagella; Future; Generations; Genes; Genome; Goals; Growth; Homeostasis; Human; In Vitro; Infection; Intervention; Investigation; Ion Pumps; Ions; Lead; Life; Life Cycle Stages; Link; Measurement; Membrane; Microbe; Modeling; Molecular; Na(+)-K(+)-Exchanging ATPase; Organism; Outcome; Parents; Pathogenesis; Pathway interactions; Performance; Phase; Phenotype; Physiological; Physiology; Plague; Plasmids; Play; Principal Investigator; Property; Proteins; Proton-Motive Force; Regulation; Research; Resistance; Role; Rotation; Sodium; Sodium-Hydrogen Antiporter; Solid; Staging; System; Therapeutic Intervention; Tissues; Virulence; Virulence Factors; Virulent; Work; Yersinia pestis; antimicrobial drug; antiporter; base; defined contribution; fitness; genetic manipulation; genome sequencing; in vivo; innovation; interest; macrophage; microbial; microorganism; mouse model; mutant; novel; overexpression; pH Homeostasis; pathogen; pathogenic bacteria; programs; research study; sodium ion; solute; trait; uptake

Program Director/Principal Investigator (Last, First, Middle): Hase, Claudia C. 1R21 AI064190-01A2 All living cells establish transmembrane electrochemical gradients with the help of primary ion pumps. Primary Na+ pumps have been discovered in many microorganisms and a transmembrane circulation of Na+ ions may play a significant role in the physiology of several pathogenic bacteria. Pathogenic bacteria are exposed to a wide range of environments both within and outside the host and have to be able to adapt to changes in the surrounding tissue to establish an infection. Although little is known about the role of the sodium cycle of energy during infection by Yersinia pestis, the presence of several sodium-dependent systems in the genome of this organism strongly suggests that this organism relies on sodium bioenergetics for at least part of its energy metabolism. We have previously hypothesized that bacterial sodium pumps involved in pH and sodium homeostasis are important for bacterial virulence and thus should provide a target for the development of a novel intervention strategy. Indeed, our preliminary results demonstrated a dramatic loss of virulence in the main sodium/proton antiporter (NhaA) mutant of Y. pestis in an animal infection model. The objectives of this application are to further define the contribution of sodium bioenergetics to Y. pestis physiology and virulence in different experimental assays. We will examine the roles of the different sodium pumps in the membrane energetics of Y. pestis by combining extensive genetic manipulations with various bioenergetic measurements. Furthermore, we will analyze the virulence traits of these mutants in vitro and in vivo to better understand the importance of these sodium pumps during the different stages of infection. Sodium bioenergetics probably plays a role in all of the various phases of the Y. pestis life cycle. Thus, the outcome of the proposed research will be of value to understanding fundamental biological concepts related to Y. pestis ecology in the lumen of its different hosts. It therefore offers great potential for application and will be of interest to a wide audience within the research community.

项目主任/主要研究者（最后，第一，中间）：Hase，Claudia C. 1R21 AI064190-01A2 所有活细胞都在初级离子泵的帮助下建立跨膜电化学梯度。在许多微生物中已经发现了初级Na+泵，并且Na+离子的跨膜循环可能在几种病原菌的生理学中起重要作用。病原菌暴露于宿主内外的广泛环境中，并且必须能够适应周围组织的变化以建立感染。虽然对鼠疫耶尔森氏菌感染过程中钠能量循环的作用知之甚少，但这种生物体基因组中存在几个钠依赖性系统，这强烈表明这种生物体至少部分依赖于钠生物能量代谢。我们以前假设，细菌钠泵参与pH和钠稳态是重要的细菌毒力，因此应该提供一个新的干预策略的发展目标。事实上，我们的初步结果表明，在Y的主要钠/质子反向转运蛋白（NhaA）突变体的毒力显着损失。动物感染模型中的鼠疫。本申请的目的是进一步确定钠生物能量学对Y的贡献。在不同的实验测定中鼠疫生理学和毒力。我们将研究不同钠泵在Y细胞膜能量学中的作用。通过将广泛的基因操作与各种生物能量测量相结合，此外，我们将在体外和体内分析这些突变体的毒力性状，以更好地了解这些钠泵在不同阶段的重要性， 感染 钠的生物能量学可能在Y染色体的各个阶段都起作用。鼠疫的生命周期因此，建议的研究结果将有助于理解与Y相关的基本生物学概念。鼠疫菌在不同宿主体内的生态学因此，它提供了巨大的应用潜力，并将在研究界的广大观众感兴趣。