Quorum sensing evolution and function in mixed bacterial communities

项目总结 大多数细菌是在复杂的微生物群落中发现的，在那里群落之间的社会互动 成员塑造社区的功能和行为。细菌调节这些物质的机制之一 相互作用是通过群体感应进行的，这是一种细胞-细胞信号，调节群体中的行为 密度依赖的方式。群体感应在许多动植物病原体的致病中起作用 出于这个原因，一直是努力开发新的抗病毒疗法的目标。以前，研究 群体感应，包括感染模型，主要是使用克隆种群进行的。结果 这些研究对阐明群体感应的分子生物学是有用的，但提供了一个有限的 了解群体感应在更复杂的社区中的作用，例如来自环境的社区 和感染。对自然产生的混合微生物群落的直接研究提出了许多挑战。一个 基因组学和遗传学新技术的结合以及实验室模型或 “合成生态学”方法在非克隆细菌种群的研究方面取得了进展。《少年派》 已经开发了实验室模型来研究混合菌株和混合物种种群的群体感应 定义群体感知如何提高这些社区的存活率。这些研究的一个主要结果是 群体感应增加了对抗生素的耐药性，这一规定改变了竞争的动态 在土壤细菌菌株之间和之间。群体感应也调节抗生素的耐药性 机会致病菌铜绿假单胞菌，这种调节在抗生素治疗中可能很重要。 在感染期间。这项建议中的研究将以这些初步结果为基础，并使用实验室模型 和临床感染分离株，研究抗生素耐药性的群体感应控制。这些研究将提供一个 从机制上理解群体调节的抗生素耐药性，定义群体感应系统如何 在抗生素的选择下适应，并确定群体感应如何改变 人口中的个别成员。结果将提供一个更完整的图景，说明群体感应是如何 改变复杂社区和患者感染的人口动态。需要此信息才能 开发新的疾病治疗策略，依赖于操纵病原体的群体感应系统。 这些结果将对群体感应领域产生影响，有助于在更广泛的范围内理解社会行为 意义，以及最后，理解如何针对社会行为有效地治疗多发性微生物 感染。

PROJECT SUMMARY Most bacteria are found in complex microbial communities, where social interactions between community members shape community function and behavior. One of the mechanisms by which bacteria regulate these interactions is through quorum sensing, a type of cell-cell signaling that regulates behaviors in a population density-dependent manner. Quorum sensing contributes to pathogenesis of many plant and animal pathogens and for this reason has been the target of efforts to develop novel antivirulence therapeutics. Previously, studies of quorum sensing, including infection models, have been primarily carried out using clonal populations. Results of those studies have been useful to elucidate the molecular biology of quorum sensing but provide a limited understanding the role of quorum sensing in more complex communities such as those from the environment and infections. Direct studies of naturally occurring mixed microbial communities present many challenges. A combination of new technologies in genomics and genetics and the development of laboratory models or `synthetic ecology' approaches have advanced progress on studies of non-clonal bacterial populations. The PI has developed laboratory models to study quorum sensing in mixed-strain and mixed-species populations to define how quorum sensing promotes survival in these communities. A major result of these studies is that quorum sensing increases resistance to antibiotics and that this regulation alters the dynamics of competition among and between strains of soil bacteria. Quorum sensing also regulates antibiotic resistance in the opportunistic pathogen P. aeruginosa, and this regulation could be important in the face of antibiotic therapy during infections. The studies in this proposal will build on these preliminary results and use laboratory models and clinical infection isolates to study quorum-sensing control of antibiotic resistance. The studies will provide a mechanistic understanding of quorum-regulated antibiotic resistance, define how quorum-sensing systems adapt under selection by antibiotics, and determine how quorum sensing alters resistance phenotypes among individual members of a population. The results will provide a more complete picture of how quorum sensing alters population dynamics in complex communities and in patient infections. This information is needed to develop novel disease treatment strategies that rely on manipulating the quorum-sensing systems of pathogens. The results will have implications in the field of quorum sensing, for understanding social behavior in a broader sense, and finally, for understanding how social behaviors can be targeted for effective treatment of polymicrobial infections.