Genetic and Metabolic Determinants of Bacterial Interspecies Interactions

细菌种间相互作用的遗传和代谢决定因素

• 批准号: 10626759
• 负责人: Paul D. Straight
• 金额: $ 27.79万
• 依托单位: TEXAS A&M AGRILIFE RESEARCH
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10626759
• 关键词: Agar; Antibiotics; Area; Attention; Bacillus subtilis; Bacteria; Bacterial Genome; Biological Assay; Biological Models; Biomedical Research; CRISPR interference; Cells; Chemicals; Chloramphenicol; Chromatography; Communication; Communities; Complex; Cues; Data; Detection; Early Diagnosis; Exposure to; Foundations; Gene Cluster; Gene Expression; Genes; Genetic; Genetic Transcription; Growth; Health; Human; Human Microbiome; Knowledge; Metabolic; Metabolic Pathway; Metabolism; Microbial Biofilms; Mission; Monitor; Natural Products; Nuclear Magnetic Resonance; Pathway interactions; Phase; Physiological; Population; Population Heterogeneity; Protein Biosynthesis; Protein Synthesis Inhibitors; Reporter; Resistance; Scanning; Signal Transduction; Signaling Molecule; Slide; Streptomyces; Structure; Surface; System; Testing; United States National Institutes of Health; Work; arm; bacterial community; candidate identification; cell motility; commensal microbes; fitness; genome analysis; improved; interest; liquid chromatography mass spectrometry; metabolome; metabolomics; microbial community; nitrogen metabolism; pathogen; purine metabolism; response; ribosome profiling; small molecule; transcriptome sequencing

Interspecies interactions are the foundation of bacterial community formation and function. Through their interactions, bacteria exert powerful influences on human health as commensal microflora, pathogens, biofilms, and antibiotic producers. A prevalent form of interaction among bacterial species relies on the exchange of specialized metabolites. Commonly represented by antibiotics, these bioactive metabolites function in myriad ways to promote the fitness of the producing species. Specialized metabolites may be toxic or growth inhibitory, or alternatively, they may function as signals and cues to relay information between species in a microbial community. Despite their importance for interactions between species, there is little understanding of the mechanisms that bacteria use to sense and respond to foreign specialized metabolites. This project focuses on an early-warning system for competitors, wherein bacteria detect specialized metabolites from other species and respond by activating a surface-mobile population. This example of an adaptive physiological response to a competitor provides the bacteria an opportunity to either escape or to counterattack. This project has two specific aims. The first aim is to define the mechanisms that activate and control bacterial motility when bacteria are exposed to specialized metabolites from a competitor. In particular, this aim will focus on major changes in metabolism and the controlling genetic functions that support a transition to a mobilized population. The second aim is to identify new motility-inducing metabolites produced by competing bacteria. Previously identified inducers are protein synthesis inhibitors that stimulate motility at subinhibitory concentrations. New inducers of unknown structure will be identified from different strains of bacteria. These inducers will expand knowledge of chemical forms that induce surface mobilization and will function as chemical probes to understand the pathways to activating the mobile response. Because inducers include protein synthesis inhibitors, new candidate antibiotics may be identified among the target specialized metabolites. Overall, these studies will advance understanding of specialized metabolism in dynamic interactions between bacterial species and how a mobile response promotes competitive fitness.

种间相互作用是细菌群落形成和功能的基础。通过他们 相互作用，细菌对人类健康产生强大的影响，如肠道微生物区系，病原体， 生物膜和抗生素生产商。细菌物种之间的一种普遍的相互作用形式依赖于 特殊代谢物的交换。通常以抗生素为代表，这些生物活性代谢物 以各种方式发挥作用，促进生产物种的适应性。专门的代谢物可能有毒 或生长抑制，或者可替代地，它们可以充当信号和线索，以在 微生物群落中的物种。尽管它们对物种间的相互作用很重要， 了解细菌用来感知和响应外来特化代谢物的机制。 该项目的重点是竞争对手的早期预警系统，其中细菌检测专门 它们从其他物种中吸收代谢物，并通过激活表面移动种群来响应。的该示例 对竞争者的适应性生理反应为细菌提供了逃跑或 反击该项目有两个具体目标。第一个目标是确定激活和 当细菌暴露于竞争对手的专门代谢物时，控制细菌运动。特别是， 这一目标将集中在代谢的主要变化和控制遗传功能，支持一个 过渡到动员人口。第二个目的是鉴定产生的新的诱导运动的代谢物 竞争的细菌。以前确定的诱导剂是蛋白质合成抑制剂，刺激运动， 亚抑制浓度新的未知结构的诱导剂将从不同的菌株中鉴定出来。 细菌这些诱导剂将扩大诱导表面移动的化学形式的知识， 作为化学探针来理解激活移动的反应的途径。因为诱导剂 包括蛋白质合成抑制剂，新的候选抗生素可以在靶向的特异性抗生素中鉴定出来。 代谢物。总的来说，这些研究将促进对动态代谢中专门代谢的理解。 细菌物种之间的相互作用以及移动的反应如何促进竞争适应性。