Intra- and Inter- Species Communication in Bacteria

细菌的种内和种间通讯

• 批准号: 10529304
• 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/10529304
• 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; Learning; Life; Life Cycle Stages; 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; interspecies communication; 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.

群体感应是一种细菌的通讯过程，它依赖于细菌的产生、检测和群体感应。 对细胞外信号分子的广泛反应称为自体诱导物。仲裁感应使多组 细菌同步改变行为以响应种群密度和物种的变化 邻区社区的组成。 目的一是研究噬菌体-细菌-真核生物群体感应介导的相互作用， 进行。拟议的研究旨在探索新发现的王国间法定人数- 感知介导的通信途径，形成宿主-微生物-噬菌体相互作用。诱变， 生物测定、小分子纯化和结晶学将被用来定义机制， 它们响应宿主群体感应信息，启动它们的裂解程序。天然 从裂解的细菌细胞中释放的提示，似乎是激活细胞的关键输入。 噬菌体群体感应“窃听”程序将被纯化。更复杂的机制， 人类微生物组的噬菌体感染，受影响的细菌如何避免噬菌体感染， 将调查微生物组细菌的数量对促进健康和有害肠道微生物的影响。球队 将利用所学到的知识来指导噬菌体疗法的开发，以对抗人类疾病。 在目标2中，研究小组将对细菌生物膜的扩散过程进行成像，并发现关键成分。 群体感应控制着被称为生物膜的表面相关群落的发展，这是一种主要的生物膜。 地球上的细菌生物膜因引起感染和表面损伤而臭名昭著。 与生物膜形成不同，几乎没有人知道生物膜生活方式的后半部分，生物膜 分散该团队将开发一种新的具有光片荧光显微镜（LSFM）的成像系统 这将使得能够对生物膜分散过程进行成像。通过成像，在单细胞分辨率，细菌 退出生物膜，研究小组将发现何时发生扩散，如果细胞单独或集体离开， 无论进程是否全局同步。使用荧光报告基因进行群体感应- 控制基因，将监测扩散期间的群体感应活动。独特的和结合的 将研究不同自诱导物在驱动/抑制生物膜分散中的作用。这 aim将为操纵传播提供线索，这是细菌生命周期的关键步骤，包括全球范围内的细菌。 病原体。 相关性（参见说明）： 细菌病原体需要群体感应来进行感染。其中一个重要的实际方面是， 研究的重点是开发抗群体感应疗法，包括新的噬菌体疗法， 替代传统抗生素。