Heterogeneity in bacterial quorum sensing during infection

感染过程中细菌群体​​感应的异质性

• 批准号: 9751343
• 负责人: Timothy Miyashiro
• 金额: $ 32.06万
• 依托单位: PENNSYLVANIA STATE UNIVERSITY, THE
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9751343
• 关键词: Address; Adolescent; Animals; Bacteria; Bacterial Physiology; Behavior; Bioluminescence; Bypass; Cell physiology; Cells; Cellular Structures; Cellular biology; Data; Detection; Disease; Environment; Exhibits; Fluorescence Microscopy; Gene Expression; Gene Targeting; Genes; Genetic Transcription; Goals; Hawaiian population; Health; Heterogeneity; Human; In Vitro; Individual; Infection; Knowledge; Light; Link; Microbe; Microbial Biofilms; Microbial Genetics; Molecular; Molecular Biology; Nature; Organ; Outcome; Pathway interactions; Pattern; Phase; Phenotype; Physiological; Physiology; Population; Process; Production; Property; Regulation; Regulator Genes; Repression; Research; Signal Transduction; Small RNA; Squid; Symbiosis; System; Testing; Time; Toxin; Vibrio fischeri; Virulence; Work; base; beneficial microorganism; cell behavior; cell motility; cell type; design; fitness; hatching; host colonization; host-microbe interactions; improved; innovation; insight; intercellular communication; juvenile animal; novel; pathogen; quorum sensing; tool; trait

Quorum sensing describes the cell-signaling systems that facilitate intercellular interactions among bacteria and coordinate population-level behaviors. Quorum sensing typically alters cellular behavior by regulating gene expression. Bacteria also use quorum sensing to regulate factors important for infecting humans and other animals. There is a gap in understanding how quorum-sensing systems are integrated into the infection process. Addressing this knowledge gap is important to gain basic insight into how pathogens and beneficial microbes form stable host-microbe associations, which will inform strategies designed to control these associations through modulating quorum sensing. The overall objective of this proposal is to determine how the bacterium Vibrio fischeri uses gene-regulatory networks associated with quorum sensing during infection of its natural host, the Hawaiian squid. V. fischeri infections initially assemble within the light organ of juvenile animals, which are un-colonized at the time of hatching. V. fischeri uses quorum sensing to regulate bioluminescence, which is its symbiotic function within the squid host. The genes necessary for bioluminescence are regulated by quorum sensing. The small RNA Qrr1 is a component of this regulatory network and negatively controls bioluminescence. Guided by preliminary data, this proposal investigates how V. fischeri uses this network during host colonization by addressing three aims: 1) Understand regulation of qrr1 transcription in V. fischeri, 2) Examine V. fischeri aggregates for phenotypic heterogeneity, and 3) Evaluate how aggregation during symbiosis establishment impacts the quorum-sensing pathway. All three aims will take advantage of the innovative platform afforded by the symbiosis: fluorescence microscopy will be used to directly examine the infection process and molecular biology tools to dissect the associated quorum- sensing systems. The proposed research is significant because it will reveal important basic principles of how quorum-sensing networks function at different infection stages, which is knowledge that has broad applicability to other host-microbe interactions and provides critical insight into strategies designed to control these associations through modulating quorum sensing.

群体感应描述了促进细菌间相互作用的细胞信号系统 并协调人口水平的行为。群体感应通常通过调节 基因表达。细菌还利用群体感应来调节感染人类的重要因素， 其他动物。在理解群体感应系统是如何整合到感染中的方面存在差距 过程解决这一知识差距对于了解病原体和有益微生物如何在人类健康中发挥作用至关重要。 微生物形成稳定的宿主-微生物协会，这将为控制这些微生物的策略提供信息。 通过调节群体感应来进行关联。本提案的总体目标是确定如何 费氏弧菌在感染时使用与群体感应相关的基因调控网络， 它的天然宿主是夏威夷鱿鱼。费氏弧菌感染最初聚集在青少年的光器官中， 动物，在孵化时未定居。费氏弧菌利用群体感应来调节 生物发光，这是它在鱿鱼宿主体内的共生功能。所必需的基因 生物发光由群体感应调节。小RNA Qrr 1是这种调控的一个组成部分， 网络和负控制生物发光。在初步数据的指导下，本提案调查了 诉fischeri在宿主定殖期间通过解决三个目标来使用该网络：1）理解 在费氏弧菌中qrr 1转录，2）检查费氏弧菌聚集体的表型异质性，以及3） 评估共生建立过程中的聚集如何影响群体感应途径。所有三 aims将利用共生提供的创新平台：荧光显微镜将被 用来直接检查感染过程和分子生物学工具来解剖相关的群体- 传感系统拟议的研究是重要的，因为它将揭示重要的基本原则， 群体感应网络在不同的感染阶段发挥作用，这是一种具有广泛适用性的知识 其他宿主-微生物相互作用，并提供了关键的洞察战略，旨在控制这些 通过调节群体感应来进行关联。