Intra- and Inter- Species Communication in Bacteria

细菌的种内和种间通讯

• 批准号: 10305584
• 负责人: BONNIE L BASSLER
• 金额: $ 34.14万
• 依托单位: PRINCETON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-12-01 至 2025-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10305584
• 关键词: Affect; Antibiotics; Automobile Driving; Bacteria; Bacteriophages; Behavior; Biological Assay; Cells; Communication; Communities; Complex; Crystallography; Cues; Detection; Development; Eukaryota; Fluorescence Microscopy; Genes; Health Promotion; Human Microbiome; Image; Individual; Infection; Instruction; Investigation; Life; Life Style; Light; Lytic; Mediating; Microbe; Microbial Biofilms; Monitor; Mutagenesis; Pathway interactions; Planet Earth; Population Density; Process; Production; Reporter; Research; Resolution; Shapes; Signaling Molecule; Surface; combat; extracellular; gut microbes; human disease; imaging system; microbiome; pathogenic bacteria; programs; quorum sensing; response; small molecule

Quorum sensing is a bacterial communication process that relies on the production, detection, and group- wide response to extracellular signaling molecules called autoinducers. Quorum sensing enables groups of bacteria to synchronously alter behavior in response to changes in population density and species composition of the vicinal community. In Aim 1, an investigation of phage-bacteria-eukaryote quorum-sensing-mediated interactions will be undertaken. The proposed research seeks to explore newly-discovered inter-kingdom quorum- sensing-mediated communication pathways that shape host-microbe-phage interactions. Mutagenesis, bioassays, small molecule purification, and crystallography will be used to define the mechanisms by which phages, in response to host quorum-sensing information, launch their lytic programs. The native cue that is released from lysed bacterial cells that appears to be the key input that activates the phage quorum-sensing "eavesdropping" program will be purified. More complex mechanisms that underlie phage infections of the human microbiome, how affected bacteria avoid phage infection, how phage infection of microbiome bacteria affects health-promoting and harmful gut microbes will be investigated. The team will use what is learned to guide the development of phage therapies to combat human diseases. In Aim 2, the team will image the bacterial biofilm dispersal process and discover the key components. Quorum sensing controls the development of surface-associated communities called biofilms, a predominant form of bacterial life on Earth. Biofilms are notorious for causing infections and damage to surfaces. Unlike biofilm formation, almost nothing is known about the second half of the biofilm lifestyle, biofilm dispersal. The team will develop a new imaging system with light sheet fluorescence microscopy (LSFM) that will enable imaging of the biofilm dispersal process. By imaging, at single-cell resolution, bacteria exiting biofilms the team will discover when dispersal occurs, if cells leave individually or collectively, and whether or not the process is globally synchronized. Using fluorescent reporters to quorum-sensing- controlled genes, quorum-sensing activity during dispersal will be monitored. The unique and combined contributions of the different autoinducers in driving/suppressing biofilm dispersal will be studied. This aim will provide leads for manipulating dispersal, a key step in bacterial lifecycles incl uding those of global pathoqens. RELEVANCE (See instructions): Bacterial pathogens require quorum sensing for infection. An important practical aspect of these investigations is the development of anti-quorum-sensing therapies including new phage therapies as alternatives to traditional antibiotics.

法群传感是一个细菌通信过程，依赖于生产，检测和组 - 对称为自动诱导剂的细胞外信号传导分子的广泛反应。法定感应启用 细菌因人口密度变化而响应于种群密度和物种的变化而改变行为 替代社区的组成。 在AIM 1中，对噬菌体 - 细菌 - 核蛋白群体感应介导的相互作用的研究将 进行。拟议的研究旨在探索新发现的王朝群 传感介导的通信途径，以塑造宿主 - 微生物 - 境相互作用。诱变， 生物测定，小分子纯化和晶体学将用于通过 在响应主机群体感应信息时，哪个噬菌体启动了其裂解程序。本地人 从裂解细菌细胞释放的提示似乎是激活的关键输入 噬菌体法定感应“窃听”程序将被净化。基础的更复杂的机制 人类微生物组的噬菌体感染，如何影响细菌避免噬菌体感染，噬菌体感染如何 将研究微生物组细菌影响健康的促进和有害的肠道微生物。团队 将使用所学的知识来指导噬菌体疗法的发展来打击人类疾病。 在AIM 2中，团队将对细菌生物膜分散过程进行映像，并发现关键组成部分。 法定人数控制了称为生物膜的表面相关群落的发展，这是一个主要的 地球上细菌生命的形式。生物膜因引起感染和对表面的损害而臭名昭著。 与生物膜的形成不同，生物膜的后半部分几乎一无所知 分散。该团队将开发一个新的成像系统，该系统具有光板荧光显微镜（LSFM） 这将实现生物膜分散过程的成像。通过成像，单细胞分辨率，细菌 退出生物膜，团队将发现何时发生分散，如果细胞单独或集体离开以及 该过程是否已全球同步。使用荧光记者进行法规感应 - 将监测受控基因，分散过程中的法定感应活性。独特而结合的 将研究不同自动诱导剂在驾驶/抑制生物膜扩散方面的贡献。这 AIM将为操纵分散提供线索，这是细菌生命周期的关键步骤，包括全球 病情。 相关性（请参阅说明）： 细菌病原体需要群体传感才能感染。这些重要的实际方面 调查是开发抗Quorum-Sensing疗法，包括新的噬菌体疗法 传统抗生素的替代品。