Intra- and Inter- Species Communication in Bacteria

细菌的种内和种间通讯

• 批准号: 9962533
• 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/9962533
• 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.

群体感应是一种依赖于生产、检测和群体的细菌交流过程