Intra- and Inter- Species Communication in Bacteria

细菌的种内和种间通讯

基本信息

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
项目类别：
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

项目摘要

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通讯过程，依赖于产生、检测和群体感应。对称为自诱导剂的细胞外信号分子有广泛的反应。群体感应使群体细菌同步改变行为以响应种群密度和物种的变化邻近社区的组成。在目标 1 中，对噬菌体-细菌-真核生物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国间法定人数塑造宿主-微生物-噬菌体相互作用的传感介导的通讯途径。诱变，生物测定、小分子纯化和晶体学将用于定义机制噬菌体响应宿主群体感应信息，启动其裂解程序。当地人从裂解的细菌细胞中释放的线索似乎是激活细菌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群的噬菌体感染，受影响的细菌如何避免噬菌体感染，噬菌体如何感染将研究微生物组细菌对促进健康和有害肠道微生物的影响。团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，团队将对细菌生物膜的扩散过程进行成像并发现关键组成部分。群体感应控制着称为生物膜的表面相关群落的发展，生物膜是一种主要的生物膜。地球上细菌生命的形式。生物膜因引起感染和表面损坏而臭名昭著。与生物膜的形成不同，我们对生物膜生活方式的后半部分几乎一无所知，生物膜分散。该团队将开发一种带有光片荧光显微镜（LSFM）的新型成像系统这将使生物膜分散过程成像。通过以单细胞分辨率对细菌进行成像当细胞分散或集体离开时，团队将发现现有的生物膜，以及进程是否全局同步。使用荧光报告基因进行群体感应受控基因，扩散过程中的群体感应活动将受到监测。独特和组合将研究不同自诱导剂在驱动/抑制生物膜扩散中的贡献。这目标将为操纵扩散提供线索，这是细菌生命周期（包括全球细菌生命周期）的关键一步病原体。相关性（参见说明）：细菌病原体需要群体感应来进行感染。这些的一个重要的实际方面是研究的重点是抗群体感应疗法的开发，包括新的噬菌体疗法传统抗生素的替代品。