Emergent metabolic coordination and cell-to-cell signaling in bacterial biofilms

细菌生物膜中的紧急代谢协调和细胞间信号传导

• 批准号: 10679046
• 负责人: Arthur Prindle
• 金额: $ 38.04万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-15 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10679046
• 关键词: Antibiotics; Award; Bacillus subtilis; Bacteria; Behavior; Biological; Cells; Communication; Communities; Data; Environment; Exhibits; Feedback; Gene Expression Regulation; Goals; Individual; Ion Channel; Mediating; Metabolic; Microbe; Microbial Biofilms; Microfluidics; Microscopy; Modeling; Molecular; Nature; Organism; Property; Public Health; Quantitative Genetics; Role; Signal Transduction; System; United States National Institutes of Health; Work; antibiotic tolerance; bacterial community; cell behavior; gene regulatory network; infancy; next generation sequencing; resilience

PROJECT SUMMARY Understanding communication among bacteria is a fundamental biological problem with critical implications for public health, especially in the context of bacterial communities known as biofilms. While bacteria are single-celled organisms, biofilms can exhibit many multicellular behaviors through emergent coordination and dynamic cell-to-cell signaling. Such collective behaviors unique to biofilms contribute to their ability to tolerate antibiotics and thrive in nearly any environment. While the advent of next-generation sequencing has ushered in a new appreciation for the broad and ubiquitous roles of bacteria in nature, our understanding of their molecular mechanisms of community coordination remains in its infancy. My overarching goal is to understand how coordinated group behaviors arise in bacterial biofilm communities through previously unexplored cell-to-cell signaling mechanisms, and how these emergent behaviors impart functional community-level benefits. Specifically, over the next five years, my group will use multiscale microscopy, high-throughput approaches, and quantitative genetics to decipher how gene regulation, metabolic adaptation, and microenvironmental feedback give rise to emergent coordination and multicellular behaviors in bacterial biofilms. With this MIRA award, my group will explore these questions by focusing on model Bacillus subtilis biofilms, where we recently used a multiscale microfluidic platform to discover that biofilm bacteria can engage in ion channel-mediated electrochemical cell-to-cell signaling. This discovery, along with other unpublished phenomena discovered by my group, make B. subtilis a powerful system for investigating how emergent behaviors arise in bacterial biofilms from single-cell-level properties such as gene regulatory networks and metabolic adaptation. Our data will inform quantitative models of multicellular phenomena, which will give us a system-level understanding of multicellular behaviors in microbes, as well as suggesting new ways to control biofilms.

项目摘要 了解细菌之间的交流是一个基本的生物学问题， 对公共卫生的影响，特别是在被称为生物膜的细菌群落的背景下。而 细菌是单细胞生物，生物膜可以表现出许多多细胞行为， 紧急协调和动态细胞间信号传导。这种生物膜特有的集体行为 有助于它们耐受抗生素的能力，并在几乎任何环境中茁壮成长。虽然出现的 下一代测序已经迎来了一个新的认识，广泛和无处不在的作用， 自然界中的细菌，我们对它们群落协调的分子机制的理解仍然存在， 处于萌芽阶段。我的首要目标是了解协调的群体行为是如何在细菌中产生的。 生物膜社区通过以前未探索的细胞间信号传导机制，以及这些 紧急行为带来了功能性的社区层面的利益。具体来说，在未来五年， 我的团队将使用多尺度显微镜、高通量方法和定量遗传学， 解读基因调控、代谢适应和微环境反馈是如何产生 细菌生物膜中的紧急协调和多细胞行为。有了这个MIRA奖，我的团队 我将通过关注枯草芽孢杆菌生物膜模型来探索这些问题，我们最近使用了 多尺度微流体平台，以发现生物膜细菌可以参与离子通道介导的 电化学细胞间信号传导。这一发现，沿着其他未发表的现象 由我的团队发现的，是B subtilis是一个强大的系统，用于研究紧急行为 在细菌生物膜中产生的单细胞水平的特性，如基因调控网络， 代谢适应我们的数据将为多细胞现象的定量模型提供信息， 让我们对微生物的多细胞行为有一个系统层面的了解，并提出新的 控制生物膜的方法