Probing the role of sensory cues in the regulation of bacterial biofilm development

探讨感觉线索在细菌生物膜发育调节中的作用

• 批准号: 10714322
• 负责人: Sampriti Mukherjee
• 金额: $ 40.13万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10714322
• 关键词: 3-Dimensional; Architecture; Bacteria; Basic Science; Behavior; Biochemistry; Biological; Biological Models; Chemicals; Communities; Cues; Decision Making; Development; Environment; Fluorescence Microscopy; Goals; Individual; Knowledge; Learning; Life Style; Light; Mediating; Microbial Biofilms; Molecular; Molecular Biology; Multi-Drug Resistance; Nutrient; Nutrient availability; Organism; Pathway interactions; Photoreceptors; Population Density; Process; Pseudomonas aeruginosa; Regulation; Repression; Research; Role; Sensory; Signal Pathway; Signal Transduction; Stimulus; Structure; System; Virulence; Work; antimicrobial tolerance; bacterial genetics; clinically relevant; design; detection of nutrient; genome-wide; human pathogen; interdisciplinary approach; mathematical model; multidrug-resistant Pseudomonas aeruginosa; multiple drug use; novel therapeutic intervention; pathogen; programs; quorum sensing; response; sensory input; sensory integration; structural biology

PROJECT SUMMARY Bacteria have a remarkable ability to sense diverse stimuli and make regulatory decisions to elicit an appropriate response. The objective of our research program is to understand the molecular underpinnings of this cellular decision-making process during the development of three dimensional (3D) structured communities called biofilms. Biofilms represent a predominant bacterial lifestyle and are crucial for antimicrobial tolerance, virulence, and environmental persistence in diverse pathogens including multi-drug resistant Pseudomonas aeruginosa. P. aeruginosa serves as an ideal clinically relevant model system for our basic research in biofilms because it adapts to and forms biofilms in a wide variety of environments, and the biofilm matrix components in this organism are well characterized. The overarching goal of the proposed research is to define how bacteria decode and integrate sensory cues – physical, chemical and biological – over the course of the biofilm development cycle. My work has shown that light (physical cue) detected via bacteriophytochrome BphP photoreceptor mediated photo sensing and population density (biological cue) detected via RhlR mediated quorum sensing represses biofilms. Furthermore, we have discovered that nutrient availability (chemical cue) converges with quorum sensing (biological cue) to control biofilm matrix components and architecture. Over the next five years, we will build on our recent discoveries and use a multidisciplinary approach combining bacterial genetics, molecular biology, biochemistry, fluorescence microscopy, mathematical modeling, structural biology and genome-scale studies to define sensory signaling in the context of a growing biofilm. First, we will investigate how light is perceived locally and globally in heterogenous biofilms and characterize the BphP photo-sensing signaling system to understand the regulation of photo sensing in P. aeruginosa (Project 1). Second, we will dissect the CbrA-Crc nutrient-sensing pathway to learn how nutrient availability controls biofilm development (Project 2). Third, we will delineate the different ways by which RhlR mediated quorum sensing represses biofilm formation (Project 3). Finally, we will define how information from two or more distinct sensory signaling pathways are combined in the control of collective behaviors (Project 4). Our research will establish a broadly relevant framework for understanding how information encoded in diverse sensory inputs is extracted and integrated to drive collective behaviors – knowledge that is crucial for designing successful synthetic strategies to enhance or to inhibit biofilms and for developing novel therapeutic interventions.

项目摘要 细菌具有感知潜水刺激并做出调节性决定以引起适当的能力 回复。我们研究计划的目的是了解该细胞的分子基础 在开发三维（3D）结构化社区期间的决策过程称为 生物膜。生物膜代表一种主要的细菌生活方式，对于抗菌耐受性，病毒， 以及包括多药抗性假单胞菌在内的潜水病原体的环境持久性。 铜绿假单胞菌是我们生物膜基础研究的理想临床相关模型系统，因为它 在多种环境中适应并形成生物膜，其中的生物膜基质组件 有机体的特征是。拟议的研究的总体目标是定义细菌如何解码 以及在生物膜开发过程中的物理，化学和生物学的综合感觉线索 - 物理，化学和生物学 循环。我的工作表明，通过细菌植物色素BPHP光感受器检测到的光（物理提示） 通过RHL介导的法规传感器检测到的介导的照片传感器和种群密度（生物提示） 压抑生物膜。此外，我们发现养分可用性（化学提示）与 法定感应（生物提示）控制生物膜基质组件和结构。在接下来的五年中， 我们将基于我们最近的发现，并使用将细菌遗传学的多学科方法， 分子生物学，生物化学，荧光显微镜，数学建模，结构生物学和 基因组规模的研究以在生物膜增长的背景下定义感觉信号传导。首先，我们将调查 在异质生物膜中如何在本地和全球感知光，并表征BPHP的光感应 信号系统了解铜绿假单胞菌中照片传感的调节（项目1）。第二，我们会的 剖析CBRA-CRC营养感应途径，以了解营养可用性如何控制生物膜开发 （项目2）。第三，我们将描述RHL介导的群体灵敏度表示生物膜的不同方式 编队（项目3）。最后，我们将定义来自两个或更多不同的感觉信号通路的信息 合并在集体行为的控制中（项目4）。我们的研究将建立广泛相关的 理解潜水员感官输入中编码的信息的框架，并将其集成到 驱动集体行为 - 知识对于设计成功的合成策略至关重要，以增强或 抑制生物膜并开发新的治疗干预措施。