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: 9794905
• 负责人: Michael David Leslie Johnson
• 金额: $ 1.3万
• 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/9794905
• 关键词: Antibiotic Resistance; Bacteria; Copper; Goals; Growth; Immune; Laboratories; Mediating; Metals; Methods; Nosocomial Infections; Nutritional Immunity; Operon; Pathway interactions; Poisoning; Research; Streptococcus pneumoniae; Stress; Surface; System; Testing; Therapeutic; Toxic effect; cell killing; lens; macrophage; prevent; response; small molecule; tool; toxic metal; undergraduate student

Project Summary Despite having a dedicated copper export system, copper has been broadly toxic to bacteria since antiquity. Copper surfaces and tools significantly reduce nosocomial infections and during host mediated nutritional immunity (sequestering essential metals while bombarding bacterial with toxic metals), innate immune cells kill engulfed targets using copper, which is tightly regulated within the host. However, current research is limited regarding the overarching mechanisms of toxicity and the pathways used overcome copper stress in conjunction with the copper export system. The R35 that this proposal connects has the major focus of using Streptococcus pneumoniae to understand how copper is toxic and how bacteria overcome copper toxicity though the lens of the copper export operon. Furthermore, it seeks to find therapeutics that can target pathways poisoned by copper stress. The goal of this proposal is to characterize compounds that synergize with copper to kill bacteria, for which, we have preliminarily been successful. Here, Angela Rivera, an undergraduate in my laboratory, will test successful compounds determining how these compounds effect the metallo-burden of the bacteria, their efficacy in preventing bacterial growth, killing bacteria, and aiding macrophages to kill bacteria.

项目摘要 尽管有专门的铜出口系统，但铜对细菌具有广泛的毒性 自古以来铜表面和工具显著减少医院感染， 宿主介导的营养性免疫（螯合必需金属，同时轰击细菌 与有毒金属），先天免疫细胞杀死吞噬目标使用铜，这是紧密 在宿主体内进行调节。然而，目前的研究是有限的， 毒性机制和所使用的途径克服了铜胁迫， 铜出口系统。本提案所连接的R35的主要重点是使用 肺炎链球菌了解如何铜是有毒的，细菌如何克服 铜毒性通过铜输出操纵子的透镜。此外，它试图找到 可以针对铜应激中毒途径的治疗方法。本提案的目的是 表征与铜协同杀死细菌的化合物，为此，我们已经 初步取得了成功。在这里，安吉拉里维拉，我实验室的一名本科生，将测试 成功的化合物，确定这些化合物如何影响金属的负担， 细菌，它们在防止细菌生长、杀死细菌和帮助巨噬细胞 杀死细菌。