Cross-species Analysis of Bacterial Gene Networks

细菌基因网络的跨物种分析

• 批准号: 10711500
• 负责人: Jason M. Peters
• 金额: $ 37.42万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10711500
• 关键词: Address; Antibiotic Resistance; Antibiotics; Bacteria; Bacterial Genes; Bacterial Physiology; Basic Science; Beds; Behavior; CRISPR/Cas technology; Chemicals; Enteral; Enterobacter cloacae; Escherichia coli; Future; Gene Expression Regulation; Genes; Genetic; Health; Homeostasis; Human; Human Microbiome; Klebsiella pneumoniae; Life; Microbe; Pathway interactions; Pattern; Property; Regulon; Role; Stress; Study models; Testing; Work; biological adaptation to stress; gene function; gene network; genome-wide; host-microbe interactions; pathogenic bacteria; portability; promoter

PROJECT SUMMARY/ABSTRACT Rationale: Gene networks underpin all aspects of bacterial physiology. These networks mitigate antibiotic induced stress in the context of antibiotic resistance, and drive microbe-microbe and microbe-host interactions in the context of the human microbiome. Despite the central role of gene networks in maintaining viability and organizing stress responses, there have been few studies that systematically compare gene networks across bacterial species. Patterns in chemical-gene, gene-gene, and gene-promoter interactions will provide clues to gene functions, pathways, and regulons, broadening our understanding of how the genetic backgrounds of strains alter network connectivity. Objective: Here we propose a cross-species comparison of genetic and regulatory networks in three enteric species relevant to human health: Escherichia coli, Enterobacter cloacae, and Klebsiella pneumoniae. Comparisons to the well-studied model, E. coli K-12, will drive gene function discovery in E. cloacae and K. pneumoniae, as well as provide a test bed for future cross species comparisons. To facilitate these analyses, we have developed CRISPR-based tools that are easily portable across species and can be used to investigate gene function and regulation at the genome scale. We seek to uncover fundamental mechanisms of homeostasis and stress responses by identifying conserved pathways. Our basic research approach could inform strategies that target weak points in gene networks of bacterial pathogens or could be applied to examine host-modified networks in the context of the human microbiome.

项目概要/摘要 基本原理：基因网络支撑着细菌生理学的各个方面。这些网络减轻抗生素 在抗生素耐药性的背景下诱导应激，并驱动微生物-微生物和微生物-宿主相互作用 在人类微生物组的背景下。尽管基因网络在维持生存能力和 组织压力反应时，很少有研究系统地比较跨性别者的基因网络。 细菌种类。化学-基因、基因-基因和基因-启动子相互作用的模式将为以下问题提供线索： 基因功能、通路和调节子，拓宽了我们对基因背景如何影响的理解 应变改变网络连接。 目的：在这里，我们提出了三种肠道遗传和调控网络的跨物种比较。 与人类健康相关的菌种：大肠杆菌、阴沟肠杆菌和肺炎克雷伯菌。 与经过充分研究的模型大肠杆菌 K-12 的比较将推动阴沟肠杆菌和大肠杆菌的基因功能发现。 肺炎链球菌，并为未来的跨物种比较提供试验台。为了促进这些分析， 我们开发了基于 CRISPR 的工具，可以轻松跨物种移植，并可用于 在基因组规模上研究基因功能和调控。我们寻求揭示基本机制 通过识别保守途径来调节体内平衡和应激反应。我们的基础研究方法可以 提供针对细菌病原体基因网络弱点的策略或可应用于 在人类微生物组的背景下检查宿主修改的网络。