Molecular analysis of bacterial interactions

细菌相互作用的分子分析

• 批准号: 10713115
• 负责人: Neha Garg
• 金额: $ 37.38万
• 依托单位: GEORGIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10713115
• 关键词: Anabolism; Antibiotic Resistance; Antibiotics; Bacteria; Chemicals; Communities; Detection; Ecosystem; Engineering; Environment; Gene Expression; Genomics; Health; Health Promotion; Human; In Vitro; Maintenance; Mass Spectrum Analysis; Mediating; Metabolic; Methods; Molecular; Molecular Analysis; Mucous body substance; Natural Products; Nature; Observational Study; Organism; Pathway interactions; Physical environment; Play; Research; Research Personnel; Resources; Role; Shapes; Source; Structure; Work; antimicrobial; bioactive natural products; coral; innovation; interdisciplinary approach; marine; microbial; microbial community; microbiome; microorganism; microorganism interaction; programs; quorum sensing; small molecule

Microorganisms live in communities in nature. The structure of microbial communities is shaped by the interactions with neighboring organisms. These interactions are often mediated by small molecules called natural products. Biosynthesis of these natural products is tightly regulated and can be induced by several factors including microbial interactions, quorum sensing, and the presence of chemical inducers such as antimicrobial compounds, or specific metabolic precursors required for biosynthesis. Description of circumstances that activate natural product biosynthesis are crucial to unravel mechanisms of induction at the molecular level and to determine their ecological functions. The overall objectives of our research program is to understand how natural product biosynthesis is activated by specific microbial and chemical environments as well as to mimic these environments in vitro enabling discovery of new natural products and their biosynthetic pathways. We will utilize mucus-dwelling bacteria from human airways, and marine corals, both of which are sources of unique natural products to investigate natural product- mediated interspecies interactions. In the project period, we will develop and apply mass spectrometry-based workflows to 1) elucidate the role of natural products and quorum sensing in interspecies interactions in host- relevant chemical and physical environment via the use of synthetic human mucus, 2) understand how chemical inducers such as antibiotics shape microbial community structure of mucus microbiomes, and 3) characterize natural product chemical space of mucus-dwelling bacteria derived from corals, an understudied resource of bioactive natural products. The methods described in this proposal enhance detection and characterization of natural product chemical space. Thus, this work will identify new natural products with antibiotic potential, which are needed in the face of increasing antibiotic resistance and declining rate of discovery of natural products- based antibiotics. The observations from this study will illuminate the mechanistic basis for natural product-mediated microbial interactions and natural-product mediated structuring of microbial communities.

微生物生活在自然界中。微生物群落的结构是形状的 通过与邻近生物的相互作用。这些相互作用通常是由小介导的 分子称为天然产物。这些天然产物的生物合成受到严格调节，并且 可以通过微生物相互作用，法规传感和 化学诱导剂（例如抗菌化合物或特定代谢前体）的存在 生物合成所需的。激活天然产品生物合成的情况的描述 对于分子水平上的诱导机制至关重要，并确定它们 生态功能。我们研究计划的总体目标是了解自然 产品生物合成被特定的微生物和化学环境以及 在体外模仿这些环境，从而发现新天然产品及其 生物合成途径。我们将利用人类气道的粘液居住细菌和海洋 珊瑚，这两种都是独特的天然产品来源来研究天然产物的来源 - 介导的种间相互作用。 在项目期间，我们将开发并将基于质谱的工作流程应用于1） 阐明天然产物和法定感应在宿主中种间相互作用中的作用 - 相关的化学和物理环境通过使用合成人体粘液，2）了解 化学诱导剂（例如抗生素）如何形成粘液的微生物群落结构 微生物组和3）表征了粘液细菌的天然产物化学空间 源自珊瑚，这是一种研究的生物活性天然产品的资源。方法 在此提案中描述了自然产品化学化学的检测和表征 空间。因此，这项工作将确定具有抗生素潜力的新天然产品，这是需要的 面对抗生素耐药性的增加和天然产物发现率的下降 - 基于抗生素。这项研究的观察结果将阐明自然的机械基础 产品介导的微生物相互作用和自然产物介导的微生物结构 社区。