Molecular mechanisms of physical interactions between bacteria and their surroundings

细菌与其周围环境之间物理相互作用的分子机制

• 批准号: 10711408
• 负责人: Courtney Kathleen Ellison
• 金额: $ 36.84万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-18 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10711408
• 关键词: Acinetobacter; Automobile Driving; Bacteria; Bacterial Pili; Behavior; Behavioral; Biochemical; Biological Process; Biology; Biophysics; Caulobacter crescentus; Cell surface; Cells; Cellular biology; Comparative Biology; Cues; DNA; Environment; Genetic; Goals; Intracellular Space; Methods; Microbial Biofilms; Molecular; Molecular Motors; Output; Pattern; Physical environment; Physiological; Physiology; Pilum; Protein Secretion; Regulation; Research Design; Signal Transduction; Stimulus; Structure; Surface; System; Techniques; Traction; Vibrio cholerae; Virulence; Work; appendage; behavior influence; cell motility; experience; extracellular; insight; mechanical properties; model organism; molecular mechanics; nanomachine; pathogenic bacteria; protein function; protein structure; response; tool development; uptake

Project Summary To survive in diverse environments, bacteria must dynamically interact with their physical surroundings to sense and incorporate stimuli into physiological responses. Bacteria often achieve this interplay between extracellular cues and intracellular signaling by using surface-exposed nanomachines that connect the intracellular space to the cell surface. The most broadly distributed surface-exposed nanomachines are appendages called type IV pili (T4P) and evolutionarily related structures that are believed to have diverged from an ancient nanomachine found in the last universal common ancestor. T4P are highly dynamic, employing multiple molecular motors to power cycles of extension and retraction that are essential for many behaviors, making them an ideal system for understanding the dynamic exchange between cells and their physical environments. Despite their broad distribution and importance in many biological processes, little is known about the fundamental biology behind T4P dynamics, regulation, and structure. We will use a combination of genetics, cell biology, biophysics, and biochemical techniques to dissect the fundamental biology of T4P. We will employ multiple model organisms including Caulobacter crescentus, Vibrio cholerae, and Acinetobacter species that all produce T4P for a comparative biology approach across different T4P. Our prior experience and expertise working in these systems will enable us to interrogate how T4P regulatory mechanisms evolve to respond to environmental stimuli and how these regulatory differences influence behavioral outputs. Our five-year goals include understanding the basic mechanisms driving T4P dynamics, how dynamics are regulated, and the consequences of different regulatory mechanisms on bacterial behavior and physiology. This work will address several key questions, including: 1) what are the main factors influencing dynamics? 2) what mechanisms control subcellular localization and patterning? And 3) how do structural subunits of T4P determine their functional and mechanical properties to influence diverse behavioral outputs? This work will provide critical insight into T4P regulation and dynamics that will result in better understanding of the physical interactions between cells and their environments and enable the development of tools to hinder or control T4P function in the broad bacterial behaviors they elicit. The fundamental discoveries made through our study of T4P will also reveal general aspects of biology including insight into the underlying mechanics of molecular motors, the mechanisms controlling intracellular spatial organization, and the relationship between protein structure and function.

项目概要 为了在不同的环境中生存，细菌必须与其物理环境动态相互作用以感知 并将刺激纳入生理反应。细菌经常在细胞外细胞之间实现这种相互作用 通过使用表面暴露的纳米机器将细胞内空间连接到信号和细胞内信号传导 细胞表面。最广泛分布的表面暴露纳米机器是称为 IV 型的附属物 菌毛（T4P）和进化相关的结构被认为是从古代纳米机器中分离出来的 发现于最后一个普遍共同祖先。 T4P 具有高度动态性，采用多个分子马达 伸展和收缩的动力循环对于许多行为都是必不可少的，这使它们成为一个理想的系统 了解细胞及其物理环境之间的动态交换。尽管他们的广泛 在许多生物过程中的分布和重要性，人们对背后的基础生物学知之甚少 T4P 动态、调节和结构。我们将结合遗传学、细胞生物学、生物物理学和 生化技术来剖析 T4P 的基本生物学。我们将采用多种模式生物 包括新月柄杆菌、霍乱弧菌和不动杆菌，它们都能产生 T4P 不同 T4P 的比较生物学方法。我们之前在这些系统中工作的经验和专业知识 将使我们能够探究 T4P 监管机制如何演变以应对环境刺激和 这些监管差异如何影响行为输出。我们的五年目标包括了解 驱动 T4P 动态的基本机制、动态如何调节以及不同的后果 细菌行为和生理学的调节机制。这项工作将解决几个关键问题， 包括：1）影响动力学的主要因素有哪些？ 2）什么机制控制亚细胞定位 和图案？ 3）T4P的结构亚基如何决定其功能和机械性能 影响不同的行为输出？这项工作将为 T4P 监管和动态提供重要见解 这将有助于更好地理解细胞与其环境之间的物理相互作用 使得开发工具能够阻碍或控制 T4P 在其引发的广泛细菌行为中的功能。这 我们通过 T4P 研究取得的基本发现也将揭示生物学的一般方面，包括 深入了解分子马达的基本机制、控制细胞内空间的机制 组织，以及蛋白质结构和功能之间的关系。