Metal ion homeostasis in Bacillus subtilis

描述（由申请方提供）：本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。这些应对措施包括精心设计高亲和力吸收系统，从环境中获取金属。也许更重要的是，细胞重新编程它们的新陈代谢，以阻止不需要的蛋白质和酶的合成，这些蛋白质和酶将消耗有限的营养。在铁的情况下，这种“节省铁的反应”导致蛋白质组成和细胞代谢潜力的大规模变化，并对细胞生理学产生广泛的影响。保铁反应在各种生物体中已经进化了多次，并且由各种基于RNA和蛋白质的调节剂介导。在B。在枯草芽孢杆菌中，节省铁的反应需要一个调节性的小RNA，该小RNA与编码小的碱性肽的三个基因协作发挥作用。这些小的蛋白质被假定至少部分地作为RNA分子伴侣起作用。初步结果表明，对锌饥饿的反应也是复杂和多方面的。抑制非必需锌金属蛋白的合成提供了一种“锌保留反应”，并且一组替代性核糖体蛋白的表达从核糖体中置换小的含锌肽以向细胞提供锌。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损的基本功能的替代同工酶（取代）。这项提案将集中在这些和相关的适应性反应，使细胞能够有效地竞争，即使在严重的金属有限的环境中的特征。公共卫生相关性：金属离子是生命所必需的，是许多酶和电子转移过程的辅助因子。该提案旨在了解模型革兰氏阳性细菌枯草芽孢杆菌如何适应铁和锌的限制。这些研究将提供重要的见解，使革兰氏阳性病原体（如金黄色葡萄球菌，链球菌和肠球菌）的适应性过程中遇到的金属有限的环境中生存的主机。

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.