Contact-dependent signaling and DNA transposition in Burkholderia

摘要 细菌通常生活在复杂的社会微生物群落中，通常以生物膜的形式存在于表面 种类繁多，如水管、船体、植物根、昆虫、贝类、留置医疗器械和 粘膜表面。人体内生物膜的生长可导致或加重疾病，而生物膜的生长 在环境中的壁龛可以促进致病菌传播给人类和其他 动物。了解细菌如何识别、合作和与邻居竞争 多样化的环境对于制定控制微生物群落的策略至关重要 成分，以防止生物膜的发展，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， 细菌利用一个大的外源蛋白的有毒C末端来杀死或抑制邻近细菌的生长 细菌在细胞间的接触。生产一种小免疫蛋白可保护细菌免受 CDI公司。使用革兰氏阴性细菌泰兰伯克霍尔德氏菌作为模型，我们有 发现除了使用CDI系统蛋白质杀死它们的邻居外，细菌还可以使用 这些蛋白质用于信号转导，导致基因表达的变化，从而导致 产生合作行为，如形成生物膜，当邻近的细菌 被认为是‘自我’的现象，我们称之为CDS(接触依赖信号)。我们最近 发现编码泰兰巴氏杆菌CDI系统蛋白(BcpAIOB)的基因是 位于一个大型移动元件上，该元件定义了一类新的转座子。我们展示了这一点 转座子使用复制-输出-粘贴-输入机制进行移动，即复制输出步骤，这导致 一个大的(210kb)、圆形的、染色体外的“巨环”的形成需要 BCPA外蛋白，CDS表型需要形成巨环。我们现在计划 为了确定bcpAIOB基因和蛋白质表达的分子机制 编码有助于巨环的形成，这是巨环形成的分子机制 形成导致基因表达变化导致合作行为，而这一作用 制度在社会微生物群落的发展中发挥着重要作用。理解 这些系统在分子水平上的功能可能会导致新的 抗生素，阻止生物膜发育和生物膜介导疾病的新方法，以及 阻止转座子介导的抗生素耐药性传播的新方法。

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.