Metal ion homeostasis in Bacillus subtilis

枯草芽孢杆菌中的金属离子稳态

• 批准号: 8245128
• 负责人: John D Helmann
• 金额: $ 29.88万
• 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 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8245128
• 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菌枯草芽孢杆菌对金属离子饥饿的反应。当细胞缺乏铁或锌等必需金属时，它们会表现出复杂的适应性反应。这些反应包括精心设计高亲和力吸收系统以从环境中获取金属。也许更重要的是，细胞重新编程其新陈代谢，以阻止不需要的蛋白质和酶的合成，这些蛋白质和酶会消耗有限的营养物质。就铁而言，这种“缺铁反应”会导致细胞的蛋白质组成和代谢潜力发生大规模变化，并对细胞生理学产生广泛的影响。缺铁反应在各种生物体中已经进化了多次，并由各种基于 RNA 和蛋白质的调节因子介导。在枯草芽孢杆菌中，缺铁反应需要一种调节性小RNA，它与编码小碱性肽的三个基因协同发挥作用。这些小蛋白质被认为至少部分地具有 RNA 伴侣的功能。初步结果表明，对锌缺乏的反应也是复杂且多方面的。对非必需锌金属蛋白合成的抑制提供了“锌节约反应”，并且一组替代核糖体蛋白的表达取代了核糖体中小的含锌肽，为细胞提供锌。除了表达高亲和力金属离子摄取（获取）和抑制非必需金属蛋白（保留）外，细胞还表达一些可能会受到损害的基本功能的替代同工酶（替代）。该提案将重点关注这些和相关适应性反应的表征，使细胞即使在金属严重有限的环境中也能有效竞争。公共健康相关性：项目叙述金属离子对于生命至关重要，并且是众多酶促和电子转移过程的辅助因子。该提案旨在了解革兰氏阳性细菌枯草芽孢杆菌模型如何适应铁和锌的限制。这些研究将为革兰氏阳性病原体（例如金黄色葡萄球菌、链球菌和肠球菌）在宿主遇到的金属限制环境中生存的适应性过程提供重要见解。