Sodium bioenergetics in Yersinia pestis

鼠疫耶尔森氏菌的钠生物能学

基本信息

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
项目类别：
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

项目摘要

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.

计划总监/首席研究员（最后，第一，中间）：Hase，Claudia C. 1R21 AI064190-01A2 所有活细胞在原发离子泵的帮助下建立了跨膜电化学梯度。在许多微生物中已经发现了原发性Na+泵，Na+离子的跨膜循环可能在几种致病细菌的生理学中起重要作用。致病细菌暴露于宿主内外的广泛环境，必须能够适应周围组织的变化以建立感染。尽管对耶尔森氏菌感染过程中能量周期的作用知之甚少，但该生物体的基因组中几种依赖钠的系统的存在强烈表明，这种生物体依赖于钠生物能源剂至少部分能量代谢。我们以前已经假设，参与pH和钠稳态的细菌钠泵对于细菌毒力很重要，因此应该为开发新的干预策略提供目标。实际上，我们的初步结果表明，在动物感染模型中，Y. pestis的主要钠/质子抗毒剂（NHAA）突变体的毒力显着丧失。该应用的目标是进一步定义钠生物能量对不同实验测定中Y. pestis生理和毒力的贡献。我们将通过将广泛的遗传操作与各种生物能测量结果相结合，来研究不同钠泵在Y. Pestis的膜能量中的作用。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。钠生物能学可能在Pestis生命周期的所有各个阶段都起作用。因此，拟议的研究的结果将有价值地了解与Y. pestis生态学有关的基本生物学概念，其不同宿主的管腔中。因此，它为应用程序提供了巨大的应用潜力，并将吸引研究界的广泛受众。