Borrelia burgdorferi LuxS-mediated quorum sensing

描述（由申请人提供）：伯氏疏螺旋体是莱姆病的病原体，通过受感染的蜱虫叮咬传播给人类和其他温血动物。伯氏疏螺旋体感染的建立涉及细菌与多种脊椎动物宿主和节肢动物载体组织之间的许多相互作用。在感染周期的特定阶段需要不同的细菌蛋白质，而对这些蛋白质合成的精确调控对于感染的成功发生至关重要。我们发现这些螺旋体利用一种调节机制来控制蛋白质表达模式，这种机制涉及一种被称为自动诱导因子2 （AI-2）的化学信号。这个分子是由伯氏疏螺旋体LuxS蛋白产生的，我们已经证明它是一种功能性酶。我们的初步研究表明伯氏疏螺旋体可以调节LuxS的合成。在培养的伯氏疏螺旋体中添加AI-2可显著改变50多种不同蛋白的表达，其中一些蛋白的表达水平升高，另一些蛋白的表达水平降低。通过这种机制，莱姆病螺旋体种群可以同步生产感染过程所需的蛋白质。我们假设伯氏疏螺旋体在莱姆病螺旋体的自然感染周期中使用AI-2作为重要的信号分子来控制蛋白质的表达。拟开展的研究将描述细菌感染过程中LuxS的表达、伯氏疏螺旋体控制AI-2合成的机制以及AI-2调节蛋白的功能。这些研究的结果将增强我们对伯氏疏螺旋体与其宿主之间复杂相互作用的理解，并确定潜在的细菌靶点，以改进莱姆病的预防和治疗方法。

DESCRIPTION (provided by applicant): The spirochete Borrelia burgdorferi, the causative agent of Lyme disease, is transmitted to humans and other warm-blooded animals through the bite of infected Ixodes spp. ticks. The establishment of B. burgdorferi infection involves numerous interactions between the bacteria and a variety of vertebrate host and arthropod vector tissues. Different bacterial proteins are required at specific points of this infectious cycle, and precise regulation of the synthesis of such proteins is essential for successful infection to occur. We have discovered that these spirochetes utilize a regulatory mechanism to control protein expression patterns that involves a chemical signal known as autoinducer-2 (AI-2). This molecule is produced by the B. burgdorferi LuxS protein, which we have demonstrated to be a functional enzyme. Our preliminary studies suggest that B. burgdorferi can regulate LuxS synthesis. Addition of AI-2 to cultured B. burgdorferi dramatically alters the expression of more than 50 different proteins, increasing expression levels of some proteins, while decreasing expression of others. Through this mechanism, a population of Lyme disease spirochetes may synchronize production of proteins needed for infection processes. We hypothesize that B. burgdorferi uses AI-2 as an important signaling molecule to control expression of proteins during the natural infectious cycle of the Lyme disease spirochetes. The proposed studies will characterize the expression of LuxS during bacterial infection, the mechanisms by which B. burgdorferi controls synthesis of AI-2, and functions of AI-2-regulated proteins. Results from these studies will enhance our understanding of the complex interactions between B. burgdorferi and its hosts, as well as identifying potential bacterial targets for improved therapies to prevent and treat Lyme disease.