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: 10250481
• 负责人: Matthew T Cabeen
• 金额: $ 34.41万
• 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/10250481
• 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.

项目摘要 细菌可以在较广泛的快速变化环境中生长和分裂，适应苛刻 通过感应外部压力源并应用该信息来安装适当的响应来进行条件。压力- 传感过程与人类健康有关：具有活化应激反应的致病细菌较少 容易受到许多抗菌治疗的影响，每年有近100,000名美国人死于 耐药细菌。实际上，环境抗生素是一种应激源（其中许多）细菌细胞 很容易回应。一个持续的挑战是，尽管环境的分子成分 压力响应系统是众所周知的，几乎没有发现这些压力反应的动态 随着时间的流逝，特别是在单个细胞中。 PI将细菌遗传学与微流体技术相结合到 直接观察在紧密控制的环境应力条件下单细胞谱系的响应， 揭示应力响应系统能够以不同的方式引起几种不同的反应 取决于细胞中存在哪些应力传感器的动力学。这些结果提出了额外的基本 问题。位于细胞质中的应激感应蛋白如何有效地响应应激源的发作 那在牢房外？应力反应蛋白的哪些分子特征指定应力源 响应和动态响应模式？不同的动态应力反应如何 模式在不利条件下有助于细胞适应性和存活？拟议的研究解决了这些 通过利用枯草芽孢杆菌作为环境的高度处理模型来提出问题 压力。通过将经典细菌遗传学，分子技术，荧光显微镜和 微流体技术，这些研究将对原则产生新的，更机械的理解 控制细菌细胞如何感知环境压力，处理这些感觉输入并产生有效 回复。结果将对理解压力反应的一般特征具有广泛的影响 在许多生物系统中。他们还将提供知识，这些知识对于设计抗菌剂很有用 干扰环境压力感应的治疗策略。