The mechanism of bistable motility gene expression in Bacillus subtilis.

枯草芽孢杆菌双稳态运动基因表达机制。

• 批准号: 8496079
• 负责人: Daniel B Kearns
• 金额: $ 27.57万
• 依托单位: TRUSTEES OF INDIANA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-15 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8496079
• 关键词: Alleles; Antibiotic Therapy; Area; Autolysin; Bacillus subtilis; Bacteria; Bacterial Antibiotic Resistance; Binding; Biological Models; Cells; Chromosomes; Competence; Complex; Coupled; DNA-Directed RNA Polymerase; Data; Development; Distant; Environment; Epigenetic Process; Escherichia coli; Exhibits; Failure; Feedback; Flagella; Flagellin; Fluorescence-Activated Cell Sorting; Fluorescent in Situ Hybridization; Gene Expression; Gene Expression Profile; Gene Expression Regulation; Genealogy; Genes; Genetic Models; Genetic Screening; Genetic Transcription; Goals; Gram-Negative Bacteria; Growth; Heterogeneity; Individual; Kinetics; Location; Measures; Mediating; Molecular Genetics; Noise; Operon; Organism; Pathogenesis; Population; Population Control; Property; Proteins; Regulation; Relative (related person); Reporter Genes; Research; Sigma Factor; Signal Transduction; Source; Structure; Swimming; Switch Genes; System; Testing; Transcript; Virulence; Work; cell motility; cell type; environmental change; gain of function; information gathering; kinetosome; loss of function; novel; pathogen; progenitor; promoter; public health relevance; response; three dimensional structure; tool

DESCRIPTION (provided by applicant): Bacterial populations, once thought to be uniform, are in fact heterogeneous mixtures of distinct cell types that become apparent when studied at the level of individual cells. Bistable (ON/OFF) gene expression epigenetically results in cell type differentiation and creates subpopulations predisposed to exploit/survive environmental change. Here we explore the unique features of the bistable expression of motility genes in Bacillus subtilis that generates mixed populations of single motile cells and non-motile chains through an epigenetic mechanism. We will measure the kinetics of switching between motility-ON and motility-OFF states and the inheritance of each state during growth. We will determine the mechanism by which the alternative sigma factor CD is controlled by both a gradual decline in transcript levels along a 27 kb operon, and regulation in response to flagellar assembly, to produce bistable gene expression. Finally, we will determine the mechanism by which a developmental regulator of unknown function, SwrA, biases the proportion of the population that is in an ON or OFF state. Motility and its control has been long-studied in Gram negative bacteria like E. coli and we intend to elevate the evolutionarily distant Gram positive B. subtilis to a premiere model system for the discovery of new paradigms of motility gene regulation. Bistability is an important new area of prokaryotic research that changes the way we think about bacterial populations. The information we gather will be directly relevant to bacterial development, antibiotic therapy, virulence gene expression, and bacterial pathogenesis.

描述（由申请人提供）：曾经被认为是统一的细菌种群实际上是不同细胞类型的异质混合物，这些混合物在单个细胞水平上进行研究时会变得显而易见。双态（开/关）基因表达在表观遗传上导致细胞类型分化，并产生易于利用/生存的环境变化的亚群。在这里，我们通过表观遗传机制探索了枯草芽孢杆菌中运动基因的双态表达的独特特征，该动力基因在枯草芽孢杆菌中产生了单运动细胞和非运动链的混合种群。我们将衡量运动能力和运动状态之间切换的动力学以及在增长过程中每个状态的遗传。我们将确定替代Sigma因子CD沿27 Kb操纵子逐渐下降的替代Sigma因子CD的控制，以及对鞭毛组装的响应调节，以产生双轴基因表达。最后，我们将确定未知功能的发育调节剂SWRA的机制偏向于处于野外或关闭状态的人群的比例。运动及其控制已在革兰氏阴性细菌（如大肠杆菌）等革兰氏阴性细菌中进行了长期研究，我们打算将进化的革兰氏片阳性枯草芽孢杆菌升至首映模型系统，以发现新的运动基因调节范式。双重性是原核生物研究的重要新领域，它改变了我们对细菌种群的看法。我们收集的信息将与细菌发育，抗生素疗法，毒力基因表达和细菌发病机理直接相关。