Metal ion homeostasis in Bacillus subtilis

枯草芽孢杆菌中的金属离子稳态

• 批准号: 8054742
• 负责人: John D Helmann
• 金额: $ 29.89万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-02-01 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8054742
• 关键词: ATP-Binding Cassette Transporters; Affinity; Bacillus subtilis; Biochemical; Biochemical Genetics; Cell physiology; Cells; Collaborations; Communities; Complex; Cytoplasm; Development; Electron Transport; Elements; Enterococcus; Environment; Enzymes; Functional RNA; Funding; GTP Cyclohydrolase; Gene Expression; Genes; Genetic; Goals; Gram-Positive Bacteria; Grant; Health; Homeostasis; Ions; Iron; Isoenzymes; Life; Mediating; Metabolic; Metabolism; Metalloproteins; Metals; Microbial Biofilms; Modeling; Molecular; Molecular Chaperones; Nutrient; Operon; Organism; Peptides; Physiological; Play; Process; Proteins; Proteomics; RNA; Regulon; Repression; Research; Ribosomal Proteins; Ribosomes; Role; Small RNA; Staphylococcus aureus; Starvation; Streptococcus; Surface; System; Testing; Time; Zinc; base; cofactor; deprivation; fitness; insight; metalloregulatory protein; methionyl aminopeptidase; paralogous gene; pathogen; peptide deformylase; response; sensor; trafficking; transcriptomics; uptake

DESCRIPTION (provided by applicant): This proposal investigates the responses of the model Gram positive bacterium Bacillus subtilis to metal ion starvation. When cells are starved for essential metals, such as iron or zinc, they express complex adaptive responses. These responses include the elaboration of high affinity uptake systems to obtain metals from the environment. Perhaps even more important, cells reprogram their metabolism to block the synthesis of unneeded proteins and enzymes that will consume the limiting nutrient. In the case of iron, this "iron-sparing response" leads to large scale changes in the protein composition and metabolic potential of the cell and has wide-ranging ramifications for cell physiology. Iron-sparing responses have evolved multiple times in various organisms and are mediated by a variety of RNA- and protein-based regulators. In B. subtilis, the iron-sparing response requires a regulatory, small RNA that functions in collaboration with three genes encoding small, basic peptides. These small proteins are postulated to function, at least in part, as RNA chaperones. Preliminary results suggest that the response to zinc starvation is also complex and multifaceted. Repression of the synthesis of non-essential zinc metalloproteins provides a "zinc-sparing response" and the expression of a set of alternative ribosomal proteins displaces small, Zn-containing peptides from the ribosome to provide zinc for the cell. In addition to the expression of high affinity metal ion uptake (acquisition) and the repression of non-essential metalloproteins (sparing), cells also express alternative isozymes for some essential functions that might otherwise be compromised (substitution). This proposal will focus on the characterization of these and related adaptive responses that enable cells to compete effectively even in severely metal-limited environments. PUBLIC HEALTH RELEVANCE: Project Narrative Metal ions are essential for life and function as cofactors for numerous enzymatic and electron transfer processes. This proposal seeks to understand how the model Gram positive bacterium Bacillus subtilis adapts to limitation for iron and zinc. These studies will provide significant insights into the adaptive processes which enable Gram positive pathogens (e.g. Staphylococcus aureus, streptococci, and enterococci) to survive in the metal-limited environments encountered in the host.

描述（由申请人提供）：该提案研究了模型革兰氏阳性细菌对金属离子饥饿的反应。当细胞饥饿的基本金属（例如铁或锌）时，它们会表达复杂的自适应反应。这些反应包括阐述高亲和力摄取系统以从环境中获取金属。也许更重要的是，细胞重新编程其代谢，以阻止将消耗限制营养素的不需要蛋白质和酶的合成。在铁的情况下，这种“避免铁的反应”会导致细胞的蛋白质组成和代谢潜力的大规模变化，并且具有广泛的细胞生理分析。在各种生物体中，避免铁的反应已经多次发展，并由各种基于RNA和蛋白质的调节剂介导。在枯草芽孢杆菌中，避免铁的反应需要一个调节性的小RNA，该RNA与编码小的基本肽的三个基因合作起作用。这些小蛋白质被认为至少部分作为RNA伴侣发挥作用。初步结果表明，对锌饥饿的反应也很复杂且多方面。对非必需锌金属蛋白的合成的抑制提供了“锌的反应”，一组替代核糖体蛋白的表达可置换核糖体含有Zn的小肽，从而为细胞提供锌。除了表达高亲和力金属离子摄取（采集）和非必需金属蛋白（备件）的抑制外，细胞还表达了可能受到损害的某些必需功能的替代同工酶（替代）。该提案将集中于这些和相关的自适应反应的表征，这些反应使细胞甚至在严重的金属有限环境中也能够有效竞争。公共卫生相关性：项目叙事金属离子对于众多酶和电子转移过程的辅助因子至关重要。该提案试图了解模型革兰氏阳性细菌枯草菌如何适应铁和锌的限制。这些研究将提供对适应过程的重要见解，这些过程使革兰氏阳性病原体（例如金黄色葡萄球菌，链球菌和肠球菌）可以在宿主遇到的金属限制环境中生存。