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

• 批准号: 10436163
• 负责人: Josephine R Chandler
• 金额: $ 36.81万
• 依托单位: UNIVERSITY OF KANSAS LAWRENCE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-30 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10436163
• 关键词: Animals; Antibiotic Resistance; Antibiotic Therapy; Antibiotics; Bacteria; Bacterial Infections; Behavior; Clinical; Communities; Complex; Disease; Ecology; Environment; Evolution; Genetic; Genomics; Goals; Individual; Infection; Infection Control; Laboratories; Modeling; Molecular Biology; Pathogenesis; Patients; Phenotype; Plants; Population; Population Density; Population Dynamics; Pseudomonas aeruginosa; Regulation; Resistance; Role; Severities; Shapes; Social Behavior; Social Interaction; Soil; System; Therapeutic; bacterial community; cell type; effective therapy; intercellular communication; laboratory development; member; microbial community; new technology; novel; opportunistic pathogen; pathogen; quorum sensing; treatment strategy

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.

项目概要 大多数细菌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 相互作用是通过群体感应实现的，这是一种调节群体行为的细胞间信号传导 密度依赖方式。群体感应有助于许多植物和动物病原体的发病机制 因此，它一直是开发新型抗毒疗法的努力目标。此前，研究 群体感应，包括感染模型，主要是使用克隆群体进行的。结果 其中一些研究有助于阐明群体感应的分子生物学，但提供的信息有限 了解群体感应在更复杂的群落（例如环境中的群落）中的作用 和感染。对自然存在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的开发或 “合成生态学”方法在非克隆细菌群体的研究方面取得了进展。 PI 开发了实验室模型来研究混合菌株和混合物种群体中的群体感应 定义群体感应如何促进这些社区的生存。这些研究的一个主要结果是 群体感应增加了对抗生素的耐药性，这种调节改变了竞争的动态 土壤细菌菌株之间。群体感应还调节抗生素耐药性 机会性病原体铜绿假单胞菌，这种调节在面对抗生素治疗时可能很重要 感染期间。本提案中的研究将建立在这些初步结果的基础上并使用实验室模型 和临床感染分离株，以研究抗生素耐药性的群体感应控制。这些研究将提供 对群体调节抗生素耐药性的机制理解，定义群体感应系统如何 适应抗生素的选择，并确定群体感应如何改变耐药表型 人口中的个体成员。结果将提供关于群体感应如何进行的更完整的描述 改变复杂社区和患者感染中的人口动态。需要此信息 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。 研究结果将对群体感应领域产生影响，有助于更广泛地理解社会行为 意义，最后，了解如何针对社会行为来有效治疗多种微生物 感染。