Heterogeneity in bacterial quorum sensing during infection

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。 并协调种群层面的行为。群体感应通常通过调节 基因表达。细菌还使用群体感应来调节对感染人类和 其他动物。在理解群体感应系统如何整合到感染中方面存在差距。 进程。解决这一知识差距对于基本了解病原体和有益于 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依据 通过调制法定人数感知进行关联。这项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 它的自然宿主夏威夷鱿鱼。V.FISHERI感染最初聚集在幼虫的光器官内 在孵化时未被殖民的动物。V.FISCHERI使用法定人数感应来调节 生物发光，这是它在鱿鱼宿主内的共生功能。所需的基因 生物发光是由群体感应调节的。小RNA Qrr1是这种调控的一个组成部分 网络，并负面控制生物发光。在初步数据的指导下，这项提案调查了 V.费斯切里在寄主定植期间通过以下三个目标使用这个网络：1)了解 Qrr1转录；2)检测裂叶云杉聚合体的表型异质性；3) 评估共生建立过程中的聚集如何影响群体感应途径。三个都是 AIMS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，以剖析相关的仲裁- 传感系统。这项拟议的研究意义重大，因为它将揭示如何 群体感知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 对其他宿主-微生物的相互作用，并提供了关键的洞察力，旨在控制这些 通过调制法定人数感知进行关联。

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.