Chemical Biology Approaches to Investigate Cell-Signaling and Competition in Complex Bacterial Communities

研究复杂细菌群落中细胞信号传导和竞争的化学生物学方法

• 批准号: 10377674
• 负责人: Yiftah Talgan
• 金额: $ 15.75万
• 依托单位: UNIVERSITY OF NEVADA RENO
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10377674
• 关键词: Acute Disease; Architecture; Attenuated; Award; Bacteria; Behavior; Biological Process; Biology; Chemicals; Chronic Disease; Communication; Communities; Complex; Detection; Development; Digestion; Food; Foundations; Genetic; Goals; Health; Human; Human Microbiome; Infection; Knowledge; Microbiology; Mission; Molecular; Pathway interactions; Peptides; Phenotype; Play; Population; Population Density; Prevention; Process; Production; Public Health; Quality of life; Research; Role; Shapes; Signal Transduction; Signaling Molecule; Techniques; Testing; United States National Institutes of Health; bacterial community; base; disease diagnosis; improved; innovation; intercellular communication; interspecies communication; novel strategies; prevent; programs; quorum sensing; structural biology

The complex architectures of bacterial communities in their natural niches hinders our understanding of the interspecies interactions that shape the overall population composition. The critical role bacteria play in human health, either by carrying out essential processes such as food digestion or through invasive infections that cause diverse chronic and acute diseases, highlight the need to develop new approaches that will enable us to study complex bacterial populations, such as the human microbiome. Failing to do so, will likely hinder further advancement in the field of sociomicrobiology and consequently prevent the development of novel strategies to harness bacterial behaviors to improve the quality of life of millions of people worldwide. The long-term goal of the research program is to utilize bacterial communication pathways to study complex bacterial communities in their natural niches. To this end, in the past two and a half years, the quorum sensing (QS) circuits of a variety of bacterial species were studied and peptide- based QS modulators with diverse activity profiles were developed. The goals for the next three years are to expand the chemical toolbox available for QS modulation and utilize the developed QS modulators to probe the effects QS has on the overall population composition of complex bacterial communities. The central hypothesis is that QS, a cell-cell signaling mechanism that enables bacteria to assess their population density through the production, secretion and detection of signal molecules, is involved in both intra-species and inter-species bacterial communications, and has an important role in bacterial competition and thus in shaping the overall population composition of complex communities. The rationale is that once the role of QS in complex bacterial communities is determined and QS modulators capable of altering the population composition are identified, an innovative approach to harness bacteria to improve human health could be developed. Guided by strong scientific premise and preliminary results, including results obtained in the first two and a half years of this award, this hypothesis will be tested by combining traditional genetic microbiology along with chemical biology techniques and structural biology analysis of peptide-based probes to uncover the role of QS in complex bacterial communities. The approach is innovative, in the applicant's opinion, because it represents a substantial departure from the status quo by focusing on the effect QS has on inter-species communication and competition, rather than on the role QS circuits play in intra-species communication. The proposed research is significant because it is expected to both define the role bacterial communication play in determining the overall population composition, and provide a novel strategy to harness bacterial behavior to promote productive processes and attenuate harmful phenotypes to ultimately improve the overall quality of life of millions of people worldwide.

细菌群落在其自然生态位中的复杂结构阻碍了我们对 物种间的相互作用决定了整个种群的组成。细菌扮演的关键角色 在人类健康中，无论是通过进行食物消化等基本过程，还是通过侵入性的 导致各种慢性和急性疾病的感染，突出了开发新方法的必要性 这将使我们能够研究复杂的细菌种群，例如人类微生物组。未能做到 因此，这可能会阻碍社会微生物学领域的进一步发展， 开发利用细菌行为的新策略，以改善数百万人的生活质量。 世界各地的人们。该研究计划的长期目标是利用细菌通讯 研究自然生态位中复杂细菌群落的途径。为此，在过去的两个和 半年的时间里，研究了各种细菌物种的群体感应（QS）回路，并研究了肽- 开发了具有不同活性特征的基于QS的调节剂。未来三年的目标是 扩展可用于QS调节的化学工具箱，并利用开发的QS调节剂， 探讨QS对复杂细菌群落总体种群组成的影响。的 中心假设是QS，一种使细菌能够评估其 通过生产，分泌和检测信号分子的人口密度，参与了这两个 种内和种间细菌通信，并在细菌的传播中发挥重要作用。 竞争，从而塑造复杂社区的整体人口构成。的理由 一旦确定了QS在复杂细菌群落中的作用， 改变人口组成的确定，一个创新的方法来利用细菌，以改善 人类健康才能发展。以强有力的科学前提和初步成果为指导，包括 在这个奖项的前两年半获得的结果，这一假设将通过结合 传统的遗传微生物学沿着化学生物学技术和结构生物学分析， 基于肽的探针，以揭示QS在复杂细菌群落中的作用。该方法是 在申请人看来，这是创新的，因为它代表了对现状的实质性偏离， 关注QS对物种间交流和竞争的影响，而不是QS的作用 电路在物种间的交流中起着重要作用。这项研究的重要性在于， 确定细菌传播在决定总体群体组成中的作用， 提供了一种新的策略来利用细菌的行为，以促进生产过程和减弱 有害的表型，以最终改善全球数百万人的整体生活质量。