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Heterogeneity in bacterial quorum sensing during infection

感染过程中细菌群体感应的异质性

基本信息

批准号：
10456610
负责人：
Timothy Miyashiro
金额：
$ 5.81万
依托单位：
PENNSYLVANIA STATE UNIVERSITY, THE
依托单位国家：
美国
项目类别：
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/10456610
关键词：
Address Adolescent Animals Bacteria Bacterial Physiology Behavior Bioluminescence Bypass Cell physiology Cells Cellular Structures Cellular biology Data Detection Disease Environment Euprymna scolopes 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

项目摘要

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之间细胞间相互作用的细胞信号系统并协调人口层面的行为。群体感应通常通过调节来改变细胞行为基因表达。细菌还利用群体感应来调节对感染人类和其他动物。对群体感应系统如何整合到感染中的理解存在差距过程。解决这一知识差距对于获得关于病原体和有益菌如何产生基本了解非常重要。微生物形成稳定的宿主-微生物关联，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。该提案的总体目标是确定如何费氏弧菌在感染过程中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幼年的光器官内孵化时尚未定殖的动物。 V. fischeri 使用群体感应来调节生物发光，这是其在鱿鱼宿主内的共生功能。所必需的基因生物发光受群体感应调节。小 RNA Qrr1 是该调节的一个组成部分网络并负控制生物发光。该提案以初步数据为指导，研究了如何 V. fischeri 在宿主定殖期间使用该网络来实现三个目标：1）了解 V. fischeri 中的 qrr1 转录，2) 检查 V. fischeri 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。全部三个目标将利用共生提供的创新平台：荧光显微镜将用于直接检查感染过程和分子生物学工具来剖析相关群体传感系统。拟议的研究意义重大，因为它将揭示重要的基本原则群体感知网络在不同的感染阶段发挥作用，这是具有广泛适用性的知识其他宿主-微生物相互作用，并为旨在控制这些相互作用的策略提供了重要的见解通过调节群体感应来进行关联。