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: 10798429
• 负责人: Paul D. Straight
• 金额: $ 11.03万
• 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/10798429
• 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发挥作用的基础。通过他们的 通过相互作用，细菌作为共生微生物区系、病原体、 生物膜和抗生素生产商。细菌物种间相互作用的一种普遍形式依赖于 交换专门的代谢物。通常以抗生素为代表的这些生物活性代谢物 以各种方式促进生产物种的适合性。专门的代谢物可能是有毒的 或生长抑制，或者可替代地，它们可以作为信号和提示来在 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，但几乎没有 了解细菌用来感知和响应外来专门代谢物的机制。 这个项目的重点是针对竞争对手的早期预警系统，其中细菌检测到专门的 来自其他物种的代谢物，并通过激活表面流动的种群来做出反应。此示例中的 对竞争对手的适应性生理反应为细菌提供了逃脱或 反击。这个项目有两个具体目标。第一个目标是定义激活和 当细菌接触竞争对手的特殊代谢物时，控制细菌的运动。特别是， 这一目标将集中在新陈代谢和控制基因功能的重大变化上，以支持 向动员人口过渡。第二个目标是识别产生的新的运动诱导代谢物。 通过相互竞争的细菌。以前已确定的诱导剂是蛋白质合成抑制剂，它能刺激运动 亚抑制浓度。将从不同的菌株中鉴定出未知结构的新诱导剂 细菌。这些诱导剂将扩展诱导表面动员的化学形式的知识，并将 发挥化学探针的作用，以了解激活移动反应的途径。因为诱导者 包括蛋白质合成抑制剂，新的候选抗生素可能被确定为专门的靶标 代谢物。总体而言，这些研究将促进对动态代谢的理解。 细菌物种之间的相互作用以及移动反应如何促进竞争适应。

项目成果

Simultaneous Two- and Three-Photon Deep Imaging of Autofluorescence in Bacterial Communities.

• DOI: 10.3390/s24020667
• 发表时间: 2024-01-20
• 期刊: Sensors (Basel, Switzerland)
• 作者: Fernández A;Classen A;Josyula N;Florence JT;Sokolov AV;Scully MO;Straight P;Verhoef AJ
• 通讯作者: Verhoef AJ

MOB rules: Antibiotic Exposure Reprograms Metabolism to Mobilize Bacillus subtilis in Competitive Interactions.

MOB 规则：抗生素暴露会重新编程代谢，以在竞争性相互作用中动员枯草芽孢杆菌。

• DOI: 10.1101/2024.03.20.585991
• 发表时间: 2024
• 期刊: bioRxiv : the preprint server for biology
• 作者: Liu,Yongjin;LaBonte,Sandra;Brake,Courtney;LaFayette,Carol;Rosebrock,AdamP;Caudy,AmyA;Straight,PaulD
• 通讯作者: Straight,PaulD