Investigating the molecules and mechanisms of bacterial cell-cell interactions

研究细菌细胞间相互作用的分子和机制

• 批准号: 10686142
• 负责人: Elizabeth Anne Shank
• 金额: $ 41.88万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10686142
• 关键词: Animals; Antibiotics; Bacillus subtilis; Bacteria; Bacterial Physiology; Behavior; Biological Models; Cell Communication; Cells; Chemicals; Communities; Complex; Cues; Development; Ecology; Environment; Genetic; Genetic Transcription; Heterogeneity; Intervention; Metabolic; Metabolism; Microbe; Microbial Biofilms; Molecular; National Institute of General Medical Sciences; Nature; Phylogenetic Analysis; Physiology; Planets; Plants; Play; Prevalence; Probiotics; Research; Role; Shapes; Signal Transduction; Soil; Source; Spatial Distribution; Specificity; Swimming; System; Therapeutic; bacterial community; extracellular; interest; member; microbial; microbial community; microbiome; secondary metabolite; tool

PROJECT SUMMARY In nature, bacteria typically exist within multispecies communities. Bacterial communities play vital roles in shaping the environment and their plant and animals. In spite of the prevalence and importance of microbial communities, important gaps still remain in our understanding of how bacteria interact within these microbiomes. Our lab’s NIGMS-relevant research is focused on investigating the chemical, molecular, and genetic mechanisms bacteria use to chemically and physically interact within multispecies communities. We focus on the soil microbiome as our model system: the soil is not one of the most phylogenetically diverse microbial environments on the planet, but soil microbes are also the source of the majority of our antibiotics and many other therapeutics. Therefore, understanding the mechanisms bacteria use to interact within this natural environment will not only provide a systems-level understanding of complex natural microbiome interactions but also provide us with potential chemical tools and therapeutic leads to manipulate bacterial behavior. These bacterially generated compounds are celled specialized or secondary metabolites. These secreted chemical cues can act as cell-cell communication signals that influence the physiology and metabolism of neighboring bacteria. They play key roles in bacterial differentiation, or the development of transcriptionally distinct, heterogeneously expressed subpopulations of cells. We focus on the soil and probiotic bacterium Bacillus subtilis, which can differentiate into cells that are making biofilm matrix, swimming, or sporulating, among others. We are interested in understanding the transcriptional specificity, ancestral lineages, and spatial distributions of this cellular heterogeneity as well as what roles specialized metabolites play in its development. We also aim to discover specialized metabolites involved in interspecies cell-cell communication to expand our understanding of chemical interactions in native microbiomes and obtain chemical tools to modulate bacterial physiology. Finally, we seek to identify the genetic and molecular mechanisms these extracellular signals use to impact bacterial transcription, heterogeneity, and metabolic activity. This research is significant because it will reveal fundamental information about the chemical and genetic mechanisms bacteria use to interact with one another. Our results will deepen our molecular understanding of cell-cell interactions within microbial communities as well as enable the development of targeted interventions to manipulate microbial behavior in environmentally and therapeutically important bacteria.

项目摘要 在自然界中，细菌通常存在于多物种群落中。细菌群落在以下方面发挥着重要作用： 塑造环境和动植物。尽管微生物的流行和重要性 然而，在我们对细菌如何在这些微生物群中相互作用的理解方面，仍然存在重要的差距。 我们实验室的NIGMS相关研究集中在研究化学，分子和遗传 细菌在多物种群落中进行化学和物理相互作用的机制。我们专注于 土壤微生物组作为我们的模型系统：土壤不是最具遗传多样性的微生物之一， 地球上的环境，但土壤微生物也是我们大多数抗生素的来源， 其他疗法。因此，了解细菌在这种自然环境中相互作用的机制， 环境不仅可以提供对复杂的自然微生物组相互作用的系统级理解， 也为我们提供了潜在的化学工具和治疗线索来操纵细菌的行为。这些 细菌产生的化合物是细胞特化的或次级代谢物。这些分泌的化学物质 线索可以作为细胞间的通信信号，影响邻近细胞的生理和代谢。 细菌它们在细菌分化或转录上不同的， 异质表达的细胞亚群。我们专注于土壤和益生菌芽孢杆菌 枯草芽孢杆菌，其可以分化成制造生物膜基质、游动或孢子形成等的细胞。 我们感兴趣的是了解转录特异性，祖先谱系和空间分布， 这种细胞的异质性以及特殊的代谢物在其发展中发挥的作用。我们还旨在 发现参与物种间细胞间通讯的特殊代谢物，以扩大我们的理解 研究天然微生物组中的化学相互作用，并获得调节细菌生理学的化学工具。 最后，我们试图确定这些细胞外信号用于影响的遗传和分子机制， 细菌转录、异质性和代谢活性。这项研究意义重大，因为它将揭示 关于细菌相互作用的化学和遗传机制的基本信息。 我们的研究结果也将加深我们对微生物群落中细胞-细胞相互作用的分子理解 能够开发有针对性的干预措施来操纵环境中的微生物行为， 重要的治疗细菌。