Diversity Supplement to Elucidating the Orchestrated Bacterial Response to Copper Toxicity

阐明细菌对铜毒性反应的多样性补充

• 批准号: 9794912
• 负责人: Michael David Leslie Johnson
• 金额: $ 3.84万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9794912
• 关键词: Bacteria; Copper; Crystallization; Laboratories; Mediating; Metals; Molecular Chaperones; Nosocomial Infections; Nutritional Immunity; Operon; Postdoctoral Fellow; Repressor Proteins; Research; Streptococcus pneumoniae; Stress; Surface; System; Toxic effect; Work; Zinc; experience; macrophage; response; sugar; tool; toxic metal

Project Summary Despite being in contact with bacteria since antiquity, copper is broadly toxic to bacteria. However, current research is limited regarding the overarching mechanisms of this toxicity. Copper toxicity is seen in practice where copper surfaces and tools significantly reduce nosocomial infections. Furthermore, during host mediated nutritional immunity (sequestering essential metals while bombarding bacterial with toxic metals), macrophages kill engulfed targets using copper, which is tightly regulated within the host. Bacteria have a copper export system consisting of a repressor, a copper chaperone, and a copper exporter. In the R35 this diversity supplement proposal is attached to, we seek to understand how bacteria evolved to interact with toxic metals. At the center of these metallo-interactions is understanding how the copper repressor works at an atomic level to regulate the operon under different metal conditions. For this proposal, Ms. Sanchez-Rosario will be working with myself, and Dr. Joseph Alvin, an experienced crystallographer and postdoctoral fellow in my laboratory, to crystalize the Streptococcus pneumoniae copper repressor protein under apo, copper, and zinc conditions. Further, she will be determining how a sugar import system that we show is regulated by the copper repressor aids in overcoming copper stress.

项目摘要 尽管自古以来就与细菌接触，但铜对细菌具有广泛的毒性。 然而，目前的研究是有限的关于这种毒性的总体机制。 铜毒性在实践中被发现，其中铜表面和工具显著降低 院内感染此外，在宿主介导的营养免疫（隔离）期间， 必需金属，同时用有毒金属轰击细菌），巨噬细胞杀死吞噬 目标使用铜，这是严格管制的主机内。细菌有铜输出 由阻遏物、铜分子伴侣和铜输出蛋白组成的系统。在R35中， 多样性补充建议是附加的，我们试图了解细菌是如何进化到 与有毒金属相互作用。在这些金属相互作用的中心是了解如何 铜阻遏物在原子水平上起作用，以调节不同金属下的操纵子 条件对于这项提案，桑切斯-罗萨里奥女士将与我和约瑟夫博士 阿尔文，一位经验丰富的晶体学家和我实验室的博士后研究员， 载脂蛋白、铜和锌条件下的肺炎链球菌铜阻遏蛋白。 此外，她将确定我们所展示的糖进口系统是如何受到监管的。 铜阻遏物有助于克服铜应激。