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：
10796553
负责人：
Josephine R Chandler
金额：
$ 1.18万
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，是社区之间的社会互动成员塑造社区功能和行为。相互作用是您的群体传感，这是一种调节人群中的细胞 - 细胞信号传导密度多种方式。因此，这是发展新颖的目标的目标。在涵盖感染模型的法定感应模型中，已经使用克隆人群进行了。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中的作用，例如环境并直接研究微生物群落新技术在基因组学中的结合以及实验室模型的发展或 “综合生态学”方法在非共同居住的研究方面取得了进步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规感如何促进这些社区的生存。群体感应传感会使对抗生素的抵抗力和调节改变竞争的动力学在土壤细菌中，群体中也调节了抗生素的抗性机会性病原体铜绿假单胞菌，这一调节在面对抗体治疗时可能很重要在感染期间。研究抗生素耐药性的临床感染分离株可提供研究。对法定符号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选择的选择，并确定法规传感如何改变表型人口的个别成员。改变复杂社区的人口动态，并在制定新的疾病治疗策略，以操纵病原体的群体感应系统。结果将在Quoruum感应领域遇到麻烦意义，最后是理解如何将社会行为定为有效治疗的目标感染。