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.

项目总结 在自然界中，细菌通常存在于多物种群落中。细菌群落在疾病中起着至关重要的作用 塑造环境和它们的动植物。尽管微生物的流行和重要性 在社区中，我们对细菌如何在这些微生物群中相互作用的理解仍然存在重大差距。 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式系统：土壤不是系统发育最多样化的微生物之一 但土壤微生物也是我们大多数抗生素和许多抗生素的来源 其他疗法。因此，了解细菌在自然界中相互作用的机制 环境不仅将提供对复杂的自然微生物群相互作用的系统级别的理解，而且 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化、特化或次生代谢物。这些分泌的化学物质 线索可以作为细胞间的通讯信号，影响周围人的生理和新陈代谢 细菌。它们在细菌分化，或在转录上不同的， 异质性表达的细胞亚群。我们专注于土壤和益生菌芽孢杆菌 枯草杆菌，它可以分化成形成生物膜基质、游泳或产孢子等的细胞。 我们对了解转录特异性、祖先谱系和空间分布感兴趣。 这种细胞异质性以及专门化代谢物在其发育过程中所扮演的角色。我们的目标还包括 发现参与物种间细胞交流的特殊代谢物，以扩大我们的理解 研究本地微生物群中的化学相互作用，并获得调节细菌生理的化学工具。 最后，我们试图确定这些细胞外信号影响的遗传和分子机制 细菌转录、异质性和代谢活性。这项研究具有重要意义，因为它将揭示 有关细菌相互作用的化学和遗传机制的基本信息。 我们的结果也将加深我们对微生物群落内细胞与细胞相互作用的分子理解 AS能够开发有针对性的干预措施，以操纵环境和环境中的微生物行为 具有重要治疗作用的细菌。