Intra- and Inter- Species Communication in Bacteria

群体感应是一种细菌通信过程，依赖于细菌的产生、检测和分组- 对称为自体诱导物的细胞外信号分子有广泛的反应。仲裁侦测支持组 细菌根据种群密度和物种的变化同步改变行为 邻里社区的组成。 在目标1中，将研究噬菌体-细菌-真核细胞群体感应介导的相互作用 要承担的责任。这项拟议的研究旨在探索新发现的跨王国法定人数- 影响宿主-微生物-噬菌体相互作用的感知中介的通信路径。诱变， 生物分析、小分子提纯和结晶学将被用来通过 这些噬菌体响应宿主的群体感应信息，启动它们的裂解程序。原住民 从裂解的细菌细胞中释放出来的信号，它似乎是激活 噬菌体群体感应“窃听”程序将被净化。更复杂的机制 噬菌体感染人体微生物群，受影响的细菌如何避免噬菌体感染，如何感染噬菌体 影响健康的微生物群和有害的肠道微生物将被调查。该队 将利用所学知识来指导噬菌体疗法的发展，以对抗人类疾病。 在目标2中，研究小组将拍摄细菌生物膜扩散过程的图像，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，生物膜是一种主要的 地球上细菌生命的形式。生物膜因对表面造成感染和破坏而臭名昭著。 与生物膜的形成不同，人们对生物膜生活方式的后半部分--生物膜几乎一无所知。 散开。该团队将开发一种带有光片荧光显微镜(LSFM)的新成像系统 这将使生物膜扩散过程的成像成为可能。通过成像，在单细胞分辨率下，细菌 研究小组将发现，如果细胞单独或集体离开，何时发生扩散，以及 进程是否全局同步。使用荧光记者来进行法定人数感应- 受控制的基因，将监测在扩散过程中的群体感应活动。独一无二的和组合的 不同的自动诱导剂在驱动/抑制生物膜扩散方面的作用将被研究。这 AIM将为操纵扩散提供线索，这是包括全球细菌在内的细菌生命周期的关键一步 病毒者。 相关性(请参阅说明)： 细菌病原体需要群体感应才能感染。其中一个重要的实践方面 研究是反群体感应疗法的发展，包括新的噬菌体疗法，如 传统抗生素的替代品。

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.