Molecular analysis of bacterial interactions

微生物生活在自然界的群落中。微生物群落的结构 通过与邻近生物的相互作用。这些相互作用通常由小的 分子称为天然产物。这些天然产物的生物合成受到严格的调控， 可以由几个因素引起，包括微生物相互作用，群体感应， 存在化学诱导物，如抗菌化合物或特定代谢前体 是生物合成所必需的。激活天然产物生物合成的环境描述 对于在分子水平上阐明诱导机制并确定其 生态功能。我们研究计划的总体目标是了解 产物生物合成被特定的微生物和化学环境激活， 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人类呼吸道和海洋中的粘液细菌 珊瑚，两者都是独特的天然产品的来源，以研究天然产品- 介导的物种间相互作用。 在项目期间，我们将开发和应用基于质谱的工作流程，以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， 相关的化学和物理环境，通过使用合成的人类粘液，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，以及3）表征粘液居住细菌的天然产物化学空间 来源于珊瑚，一种未被充分研究的生物活性天然产品资源。的方法 本提案中所描述的增强天然产物化学品的检测和表征 空间因此，这项工作将确定新的天然产物与抗生素的潜力，这是必要的， 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， 产物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.

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.