Molecular analysis of bacterial interactions

微生物生活在自然界的群落中。微生物群落的结构被塑造 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 被称为天然产物的分子。这些天然产物的生物合成受到严格的监管和 可以由几个因素诱导，包括微生物相互作用、群体感应和 存在化学诱导剂，如抗菌化合物或特定的代谢前体 生物合成所必需的。对激活天然产物生物合成的环境的描述 对于在分子水平上解开诱导机制并确定它们的 生态功能。我们研究计划的总体目标是了解 产品的生物合成被特定的微生物和化学环境激活，以及 在体外模拟这些环境，能够发现新的天然产品和它们的 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 珊瑚和珊瑚都是研究天然产品的独特天然产品的来源- 调解的种间相互作用。 在项目期间，我们将开发基于质谱学的工作流程并将其应用于1) 阐明天然产物和群体感应在寄主物种间相互作用中的作用 相关的化学和物理环境通过使用人工合成的人体粘液，2)了解 抗生素等化学诱导剂如何影响粘液微生物群落结构 微生物群；3)粘液细菌天然产物化学空间特征 源自珊瑚，是一种未被充分研究的生物活性天然产品资源。这些方法 本提案中描述的增强天然产品化学物质的检测和表征 太空。因此，这项工作将确定需要的具有抗生素潜力的新的天然产品 面对不断增加的抗生素耐药性和不断下降的天然产品发现率- 以抗生素为基础。这项研究的观察结果将阐明自然界 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.