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.

项目摘要 为了在不同的环境中生存，细菌必须动态地与其物理环境相互作用，以感知 并将刺激融入生理反应中。细菌经常在细胞外 通过使用表面暴露的纳米机器连接细胞内空间， 细胞表面。最广泛分布的表面暴露的纳米机器是被称为IV型的附属物 皮利（T4 P）和进化相关的结构，被认为是从一个古老的纳米机器分歧 在最后一个共同祖先身上发现的T4P是高度动态的，采用多个分子马达， 权力循环的延伸和收缩，是必不可少的许多行为，使他们成为一个理想的系统， 了解细胞与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，很少有人知道背后的基本生物学 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 生物化学技术来剖析T4P的基本生物学。我们将使用多种模式生物 包括新月柄杆菌、霍乱弧菌和不动杆菌属，它们都产生T4P， 不同T4P的比较生物学方法。我们在这些系统中的经验和专业知识 将使我们能够询问T4P调节机制如何演变以响应环境刺激， 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。 对细菌行为和生理的调节机制。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是什么？2)什么机制控制亚细胞定位 和模式？T4P的结构亚基如何决定其功能和力学性质 来影响不同的行为输出这项工作将提供关键的洞察T4P的调控和动力学 这将导致更好地理解细胞与其环境之间的物理相互作用， 使工具的发展，以阻碍或控制T4P的功能，在广泛的细菌行为，他们引起的。的 通过我们对T4P的研究所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。