Metal ion homeostasis in Bacillus subtilis

描述(申请人提供)：这项提案调查了模式革兰氏阳性细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。这些反应包括制定高亲和力吸收系统以从环境中获取金属。也许更重要的是，细胞重新编程自己的新陈代谢，阻止合成不需要的蛋白质和酶，这些蛋白质和酶将消耗有限的营养。在铁的情况下，这种“省铁反应”会导致细胞蛋白质组成和代谢潜力的大规模变化，并对细胞生理学产生广泛的影响。在不同的生物体中，铁的节约性反应已经进化了多次，并由各种以RNA和蛋白质为基础的调节因子介导。在枯草杆菌中，省铁的反应需要一个受调控的小RNA，它与编码小的碱性多肽的三个基因协同工作。据推测，这些小蛋白的功能至少部分是作为RNA伴侣。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“锌节约反应”，一组替代核糖体蛋白的表达取代了核糖体中含锌的小肽，为细胞提供锌。除了表达高亲和力的金属离子摄取(获取)和抑制非必需金属蛋白(Sparing)外，细胞还表达一些可能受到损害的基本功能的替代同工酶(替代)。这项建议将集中于这些和相关的适应性反应的特征，使细胞即使在严重的金属有限的环境中也能有效地竞争。公共卫生相关性：项目叙述金属离子对生命是必不可少的，并作为许多酶和电子转移过程的辅助因素发挥作用。这项建议旨在了解模式革兰氏阳性细菌枯草芽孢杆菌如何适应铁和锌的限制。这些研究将对使革兰氏阳性病原体(如金黄色葡萄球菌、链球菌和肠球菌)在宿主遇到的金属有限的环境中生存的适应过程提供重要的见解。

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.