Diversity Supplement to Elucidating the Orchestrated Bacterial Response to Copper Toxicity

项目摘要 尽管铜自古以来就与细菌接触，但它对细菌的毒性很大。 然而，目前关于这种毒性的主要机制的研究有限。 铜的毒性在实践中被看到，在那里铜表面和工具显著减少 医院感染。此外，在宿主介导的营养免疫(隔离)期间 当有毒金属轰击细菌时)，巨噬细胞被吞噬 目标使用铜，这在主机内部受到严格监管。细菌有铜的出口 由抑制子、铜伴侣和铜输出器组成的系统。在R35中，这是 多样性补充建议附后，我们试图了解细菌是如何进化到 与有毒金属相互作用。这些金属相互作用的核心是理解 铜抑制物在原子水平上对不同金属下的操纵子进行调节 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合作 阿尔文是一位经验丰富的结晶学家，也是我实验室的博士后研究员，他将 肺炎链球菌铜抑制蛋白在载脂蛋白、铜和锌条件下。 此外，她将决定我们展示的糖进口制度如何受到 铜抑制因子有助于克服铜胁迫。

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.