Quorum sensing evolution and function in mixed bacterial communities

项目摘要 大多数细菌都存在于复杂的微生物群落中，群落之间的社会相互作用 成员塑造社区功能和行为。细菌调节这些的机制之一 群体感应是一种调节群体行为的细胞间信号传导 密度依赖的方式。群体感应参与了许多动植物病原体的致病过程 并且由于这个原因，已经成为开发新的抗病毒治疗剂的努力的目标。此前，研究 包括感染模型在内的群体感应研究主要是利用克隆种群进行的。结果 这些研究有助于阐明群体感应的分子生物学， 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 和感染对天然存在的混合微生物群落的直接研究存在许多挑战。一 结合基因组学和遗传学的新技术和实验室模型的发展， “综合生态学”方法推动了非克隆细菌种群研究的进展。的PI 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， 定义群体感应如何促进这些社区的生存。这些研究的主要结果是， 群体感应增加了对抗生素的抵抗力，这种调节改变了竞争的动态 在土壤细菌的菌株之间。群体感应还调节细菌中的抗生素耐药性。 条件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。本提案中的研究将以这些初步结果为基础，并使用实验室模型 和临床感染分离株来研究群体感应控制抗生素耐药性。这些研究将提供一个 了解群体调节抗生素耐药性的机制，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 人口中的个体成员。结果将提供一个更完整的图片如何群体感应 改变了复杂社区和患者感染中的人口动态。需要这些信息， 开发依赖于操纵病原体群体感应系统的新型疾病治疗策略。 这些结果将在群体感应领域产生影响，从而在更广泛的范围内理解社会行为。 意义，最后，了解如何社会行为可以有针对性地有效治疗多微生物 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.