Contact-dependent signaling and DNA transposition in Burkholderia

伯克霍尔德氏菌中的接触依赖性信号传导和 DNA 转座

• 批准号: 10381490
• 负责人: Peggy A Cotter
• 金额: $ 38.88万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10381490
• 关键词: Animals; Antibiotic Resistance; Antibiotics; Bacteria; Behavior; Binding; Burkholderia; Cells; Communities; Community Developments; Complex; Cooperative Behavior; Cytoplasm; DNA; Development; Disease; Elements; Environment; Evolution; Gene Expression; Gene Proteins; Gram-Negative Bacteria; Growth; Horizontal Gene Transfer; Human; Immunity; Insecta; Lead; Link; Mediating; Medical Device; Microbial Biofilms; Microbiology; Modeling; Molecular; Mucous Membrane; Paste substance; Phenotype; Plant Roots; Play; Production; Proteins; Role; Shellfish; Ships; Signal Transduction; Signaling Protein; Surface; System; gene discovery; hookah; novel strategies; pathogenic bacteria; prevent; protein complex; transmission process

Abstract Bacteria typically live in complex sociomicrobiological communities, often as biofilms, on surfaces as diverse as water pipes, ship hulls, plant roots, insects, shellfish, indwelling medical devices, and mucosal surfaces. Biofilm growth in humans can cause or exacerbate disease, and biofilm growth in environmental niches can facilitate transmission of pathogenic bacteria to humans and other animals. Understanding how bacteria recognize, cooperate and compete with their neighbors in diverse environments is critical for developing strategies to control microbiological community composition, to prevent biofilm development, and to eliminate pre-existing biofilms and their consequent diseases. Contact-Dependent Growth Inhibition (CDI) is a phenomenon in which bacteria use the toxic C-terminus of a large exoprotein to kill or inhibit the growth of neighboring bacteria upon cell-cell contact. Production of a small immunity protein protects bacteria against CDI. Using the Gram-negative bacterium Burkholderia thailandensis as a model, we have discovered that in addition to using CDI system proteins to kill their neighbors, bacteria can use these proteins for signal transduction, causing a change in gene expression that leads to the production of cooperative behaviors, such as biofilm formation, when neighboring bacteria are recognized as ‘self’, a phenomenon we call CDS (for contact-dependent signaling). We recently discovered that the genes encoding the CDI system proteins in B. thailandensis (bcpAIOB) are located on a large mobile element that defines a new class of transposon. We showed that this transposon moves using a copy-out-paste-in mechanism, that the copy-out step, which results in the formation of a large (210 kb), circular, extrachromosomal ‘megacircle’, requires the activity of the BcpA exoprotein, and that megacircle formation is required for CDS phenotypes. We now plan to determine the molecular mechanisms by which the bcpAIOB genes and the proteins they encode contribute to megacircle formation, the molecular mechanisms by which megacircle formation leads to gene expression changes resulting in cooperative behaviors, and the role this system plays in the development of sociomicrobiological community development. Understanding the function of these systems at the molecular level may lead to the development of new antibiotics, new approaches to blocking biofilm development and biofilm-mediates diseases, and new approaches to blocking transposon-mediated spread of antibiotic resistance.

抽象的 细菌通常生活在复杂的社会生物学群落中，通常为生物膜，在表面上 像水管一样潜水，船体，植物根，昆虫，贝类，留置医疗设备以及 粘膜表面。人类生物膜的生长会引起或加剧疾病，生物膜生长 在环境中，生态位可以促进致病细菌向人类和其他 动物。了解细菌如何认识，教练和与邻居竞争 潜水员环境对于制定控制微生物社区的策略至关重要 组成，防止生物膜发育，并消除先前存在的生物膜及其 随之而来的疾病。接触依赖性生长抑制（CDI）是一种现象，其中 细菌使用大一色蛋白的有毒C末端杀死或抑制相邻的生长 细菌接触时细菌。产生少量免疫史蛋白可保护细菌免受 CDI。将革兰氏阴性细菌Burkholderia thailandensis作为模型，我们有 发现除了使用CDI系统蛋白杀死邻居外，细菌还可以使用 这些用于信号转导的蛋白质，导致基因表达变化，导致 当相邻细菌为生物膜形成等合作行为，例如生物膜形成 我们称为“自我”，这是一种我们称为CD（用于接触依赖的信号传导）的现象。我们最近 发现编码泰国芽孢杆菌（BCPAIOB）中编码CDI系统蛋白的基因是 位于一个定义新类Transposon的大型移动元件上。我们证明了这一点 转座子使用复制式式机制移动，即复制步骤，这导致 大型（210 kb）的形成，圆形，外染色体“巨型圆形”，需要活动的活动 CDS型需要BCPA的ofo蛋白，并且Megacircle形成是CDS型。我们现在计划 确定BCPAIOB基因和蛋白质的分子机制 编码有助于巨圆形形成，这是分子机制 形成导致基因表达变化导致合作行为，以及这一作用 系统在社会生物学群落发展的发展中发挥作用。理解 这些系统在分子水平上的功能可能导致新的发展 抗生素，阻断生物膜发育和生物膜疾病的新方法，以及 阻断转座子介导的抗生素耐药性扩散的新方法。