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，通常作为生物膜， 如水管、船体、植物根、昆虫、贝类、留置医疗器械等， 粘膜表面。人体内的生物膜生长可导致或加重疾病， 在环境小生境中，可以促进致病菌传播给人类和其他人， 动物了解细菌如何识别，合作和竞争，与他们的邻居， 不同的环境对于制定控制微生物群落的策略至关重要 组合物，以防止生物膜发展，并消除预先存在的生物膜及其 随之而来的疾病接触依赖性生长抑制（CDI）是一种现象，其中 细菌利用一个大的胞外蛋白的有毒C末端杀死或抑制邻近的细菌的生长， 细胞与细胞接触后的细菌。一种小免疫蛋白的产生可以保护细菌免受 CDI.使用革兰氏阴性细菌Burkholderia thailandensis作为模型，我们 发现除了使用CDI系统蛋白杀死它们的邻居，细菌还可以使用 这些蛋白质的信号转导，引起基因表达的变化，导致 合作行为的产生，如生物膜的形成，当邻近的细菌是 这种现象我们称之为CDS（接触依赖信号）。我们最近 发现编码B. thailandensis（bcpAIOB） 位于一个大的移动的元件上，该元件定义了一类新的转座子。我们发现这 转座子使用复制-输出-粘贴-输入机制移动，即复制步骤，其导致 一个大的（210 kb），环状，染色体外的“巨环”的形成，需要 BcpA外蛋白，且巨环形成是CDS表型所需。我们现在计划 为了确定bcpAIOB基因和蛋白质的分子机制， 编码有助于形成巨环，巨环形成的分子机制 形成导致基因表达的变化，从而导致合作行为， 系统在社会微生物群落发展中的作用。理解 这些系统在分子水平上的功能可能导致新的 抗生素，阻断生物膜发展和生物膜介导疾病的新方法， 阻断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.