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.

微生物在自然界中以群落形式生活。微生物群落的结构已形成 通过与邻近生物体的相互作用。这些相互作用通常是由小的介导的 称为天然产物的分子。这些天然产物的生物合成受到严格监管 可以由多种因素诱导，包括微生物相互作用、群体感应和 化学诱导剂的存在，例如抗菌化合物或特定的代谢前体 生物合成所需。激活天然产物生物合成的情况描述 对于在分子水平上揭示诱导机制并确定它们的作用至关重要 生态功能。我们研究计划的总体目标是了解自然 产品生物合成是由特定的微生物和化学环境激活的 在体外模拟这些环境，从而能够发现新的天然产物及其 生物合成途径。我们将利用来自人类呼吸道和海洋的粘液细菌 珊瑚，两者都是独特的天然产物的来源，以研究天然产物 - 介导的种间相互作用。 在项目期间，我们将开发并应用基于质谱的工作流程：1) 阐明天然产物和群体感应在宿主种间相互作用中的作用 通过使用合成人体粘液了解相关的化学和物理环境，2) 了解 抗生素等化学诱导剂如何塑造粘液的微生物群落结构 微生物组，3) 表征粘液细菌的天然产物化学空间 源自珊瑚，一种未经充分研究的生物活性天然产品资源。方法 该提案中描述的增强天然产物化学品的检测和表征 空间。因此，这项工作将确定具有抗生素潜力的新天然产物，这是我们所需要的 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现象的机制基础 产品介导的微生物相互作用和天然产物介导的微生物结构 社区。