Quorum sensing evolution and function in mixed bacterial communities

混合细菌群落中的群体感应进化和功能

基本信息

批准号：
10727000
负责人：
Josephine R Chandler
金额：
$ 1.2万
依托单位：
UNIVERSITY OF KANSAS LAWRENCE
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-07-30 至 2025-05-31
项目状态：
未结题

项目摘要

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.

项目摘要大多数细菌都在复杂的微生物群落中发现，社区之间的社交互动成员塑造社区功能和行为。细菌调节这些的机制之一相互作用是通过法定传感的，这是一种调节种群行为的细胞细胞信号传导密度依赖性方式。法定感应有助于许多动植物病原体的发病机理因此，一直是开发新型抗毒素治疗剂的努力的目标。以前，研究包括感染模型在内的法定感应的主要是使用克隆种群进行的。结果这些研究中有助于阐明法规传感的分子生物学，但提供了有限的了解法定人感应在更复杂的社区（例如环境的社区）中的作用和感染。对自然发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以及实验室模型的发展或 “综合生态学”方法在非共鸣细菌种群的研究方面取得了进步。 pi 已经开发了实验室模型，以研究混合株和混合物种种群中的法定感应定义法定人数如何促进这些社区的生存。这些研究的主要结果是法定感应增加了对抗生素的抵抗力，并且这种调节会改变竞争的动力学土壤细菌菌株之间和之间。法群传感还调节了抗生素耐药性机会性病原体铜绿假单胞菌，面对抗生素治疗可能很重要在感染期间。该提案中的研究将基于这些初步结果，并使用实验室模型和临床感染分离株以研究抗生素耐药性的法定感应控制。研究将提供对法定调节的抗生素耐药性的机械理解，定义了法定感应系统的方式适应抗生素的选择，并确定法规传感如何改变抗药性表型人口的个人成员。结果将提供更完整的图案，说明法规如何感应改变复杂社区和患者感染的人口动态。需要此信息制定新的疾病治疗策略，这些策略依赖于操纵病原体的群体感应系统。结果将对法定人类感知的领域产生影响，以了解更广泛的社会行为意义，最后是了解如何将社会行为定为有效治疗多数菌感染。