Stress sensing and processing by bacterial cytoplasmic megacomplexes

细菌细胞质巨复合物的压力传感和处理

• 批准号: 10027912
• 负责人: Matthew T Cabeen
• 金额: $ 34.25万
• 依托单位: OKLAHOMA STATE UNIVERSITY STILLWATER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-15 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10027912
• 关键词: American; Antibiotics; Bacillus subtilis; Bacteria; Cell Lineage; Cells; Cytoplasm; Data; Defense Mechanisms; Disinfectants; Environment; Exposure to; Fluorescence Microscopy; Growth; Health; Human; Immune response; Individual; Infection; Knowledge; Modeling; Molecular; Pattern; Pharmaceutical Preparations; Process; Proteins; Sensory Process; Specific qualifier value; Stress; System; Techniques; Time; antimicrobial; bacterial genetics; biological adaptation to stress; biological systems; drug resistant bacteria; fitness; microbial; microfluidic technology; pathogenic bacteria; response; sensor; sensory input; stressor; treatment strategy

PROJECT SUMMARY Bacteria can grow and divide in a remarkably wide range of quickly changing environments, adapting to harsh conditions by sensing external stressors and applying that information to mount an appropriate response. Stress- sensing processes are relevant to human health: pathogenic bacteria with activated stress responses are less susceptible to many antimicrobial treatments, and nearly 100,000 Americans die each year from infections with drug-resistant bacteria. Indeed, environmental antibiotics are one stressor (among many) to which bacterial cells readily respond. A persistent challenge has been that, although the molecular components of the environmental stress response system are well known, little has been discovered about the dynamics of these stress responses over time, particularly in individual cells. The PI has combined bacterial genetics with microfluidic technology to directly observe the responses of single-cell lineages under tightly controlled environmental stress conditions, revealing that the stress-response system is capable of eliciting several distinct responses with different dynamics that depend on which stress sensors are present in the cell. These results raise additional fundamental questions. How do stress-sensing proteins located in the cytoplasm effectively respond to the onset of stressors that are outside the cell? Which molecular features of stress-response proteins specify the stressors they respond to and the dynamic response patterns they instigate? How do different dynamic stress-response patterns contribute to cellular fitness and survival in adverse conditions? The proposed studies tackle these questions by taking advantage of the bacterium Bacillus subtilis as a highly tractable model for environmental stress. By bringing together classical bacterial genetics, molecular techniques, fluorescence microscopy, and microfluidic technology, these studies will yield a new and more mechanistic understanding of the principles that govern how bacterial cells sense environmental stress, process those sensory inputs, and produce an effective response. The results will have broad implications for understanding the general features of stress responses across many biological systems. They will also furnish knowledge that will be useful for devising antimicrobial treatment strategies that interfere with environmental stress sensing.

项目概要 细菌可以在非常广泛的快速变化的环境中生长和分裂，适应恶劣的环境 通过感知外部压力源并应用该信息来采取适当的应对措施。压力- 传感过程与人类健康相关：具有激活应激反应的病原菌较少 易受多种抗菌药物治疗影响，每年有近 100,000 美国人死于感染 耐药细菌。事实上，环境抗生素是细菌细胞所承受的压力源之一（众多压力源之一）。 欣然回应。一个持续存在的挑战是，尽管环境的分子成分 应激反应系统是众所周知的，但关于这些应激反应的动态却知之甚少 随着时间的推移，尤其是在单个细胞中。 PI 将细菌遗传学与微流体技术相结合 直接观察单细胞谱系在严格控制的环境应激条件下的反应， 揭示压力反应系统能够引发几种不同的不同反应 动态取决于细胞中存在哪些压力传感器。这些结果提出了额外的基础 问题。位于细胞质中的应激感应蛋白如何有效应对应激源的出现 那些在细胞外？应激反应蛋白的哪些分子特征指定了它们所面对的应激源 响应以及它们引发的动态响应模式？不同的动态应激反应如何 模式有助于细胞在不利条件下的适应和生存？拟议的研究解决了这些问题 利用枯草芽孢杆菌作为环境的高度易处理模型来解决问题 压力。通过将经典的细菌遗传学、分子技术、荧光显微镜和 微流体技术，这些研究将对微流体技术的原理产生新的、更机械的理解 控制细菌细胞如何感知环境压力、处理这些感官输入并产生有效的 回复。结果将对理解压力反应的一般特征产生广泛的影响 跨越许多生物系统。他们还将提供有助于设计抗菌药物的知识 干扰环境压力感知的治疗策略。