Quorum sensing in Pseudomonas aeruginosa

项目摘要 群体感应是一种细胞间通讯的形式，允许细菌群体的成员 以细胞密度依赖的方式协调合作活动。群体感应已经被证明 在铜绿假单胞菌和其他病原体的毒力中起重要作用，铜绿假单胞菌具有 成为研究群体感应、交流与合作等基本生物学原理的典范 梗概.我们对铜绿假单胞菌酰基高丝氨酸内酯群体感应的研究是努力的基础 旨在操纵感染期间的群体感应，在复杂的微生物群落中， 生物技术应用。我们一直并将继续对基本机制感兴趣， 群体感应，有利于群体感应控制基因表达的选择压力，以及成本 和群体感应的好处。群体感应功能控制和协调 合作行为很明显，协同性是一种进化的生物现象，但 关于允许稳定的协同性的选择力的相当大的争议。什么是成本和 协同性的好处，以及通过群体感应控制协同性的可能优势是什么？ 在过去的五年里，我们在分子水平上的理解上取得了巨大的进步， 合作是稳定的铜绿假单胞菌和我们如何可以不稳定。这些进展是重要的， 群体生物学领域和我们对铜绿假单胞菌群体感应在某些 感染.我们的后续研究将使用分子遗传学方法来研究群体感应 控制基因表达，我们将继续引入新的技术和概念， 成为微生物研究的一个活跃领域。具体地说，我们将问一些关于 信号特异性和细菌物种相互窃听的可能性。我们将尝试定义 信号产生和接收选择性的决定因素。我们希望更好地了解 人类感染期间的群体感应，我们最初的重点是慢性肺部感染， 患有囊性纤维化的人。我们最近了解到， RhlR是铜绿假单胞菌群体感应系统的重要组成部分，是铜绿假单胞菌群体感应的关键元件。 铜绿。我们最近的工作使我们能够克服学习RhlR的主要障碍， 无法在体外进行研究。这项工作的长期愿景是了解如何和为什么群体感应 电路通常是分层的，以了解群体感应系统的多样性是如何发展到其 目前的状态，并获得一个概念框架，以解释如何沟通和合作活动， 是为了提供细菌群体活动的稳定性，以及我们如何能够利用这些知识， 操纵细菌种群。

PROJECT SUMMARY Quorum sensing is a form of cell-cell communication that allows members of bacterial populations to coordinate cooperative activities in a cell density-dependent fashion. Quorum sensing has been shown to play a significant role in the virulence of Pseudomonas aeruginosa and other pathogens, and P. aeruginosa has become a model for studies of basic biological principles of quorum sensing, communication, and cooperation in general. Our research on P. aeruginosa acyl-homoserine lactone quorum sensing is fundamental to efforts aimed at manipulating quorum sensing during infections, in complex microbial communities, and for biotechnological applications. We have been, and will continue to be, interested in basic mechanisms of quorum sensing, the selective pressures favoring quorum-sensing control of gene expression, and the costs and benefits of quorum sensing in P. aeruginosa. Quorum sensing functions to control and coordinate cooperative behaviors. It is clear that cooperativity is an evolved biological phenomenon, but there is considerable controversy about the selective forces allowing stable cooperativity. What are the costs and benefits of cooperativity, and what are the possible advantages to controlling cooperativity by quorum sensing? In the past five years we have made enormous advances in understanding at a molecular level how cooperation is stabilized in P. aeruginosa and how we can destabilize it. These advances are important to the field of population biology and to our understanding of the roles P. aeruginosa quorum sensing plays in certain infections. Our continued research will use molecular genetic approaches to investigate the quorum sensing control of gene expression, and we will continue to introduce new techniques and concepts into what has become a vibrant field of microbiological research. Specifically we will ask questions about the determinants of signal specificity and the potential for bacterial species to eavesdrop on each other. We will attempt to define the determinants of signal generation and reception selectivity. We want to better understand the role of quorum sensing during human infections with our initial emphasis on the chronic lung infections that plague people with the genetic disease cystic fibrosis. We have recently learned that one of the least understood components of P. aeruginosa quorum sensing circuitry, RhlR is a key quorum-sensing element in P. aeruginosa. Our recent work has allowed us to overcome the major obstacle in learning about RhlR, an inability to study it in vitro. The long term vision of this work is to understand how and why quorum sensing circuits are often layered, to understand how the diversity of quorum sensing systems has evolved to its current state, and to attain a conceptual framework to explain how communication and cooperative activities are wired to provide stability of bacterial group activities and how we might be able to use the knowledge to manipulate bacterial populations.