Novel Two Component Regulation of Quorum Sensing & Secondary Metabolite Production in Bacteria

群体感应的新型二元调控

• 批准号: 1035157
• 负责人: Leland Pierson III
• 金额: $ 20.1万
• 依托单位: Texas A&M AgriLife Research
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2013-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1035157&HistoricalAwards=false
• 关键词: Novel; Two; Component; Regulation; Quorum

ABSTRACTLELAND S. PIERSON IIIPROPOSAL # NSF 0545804TITLE: Novel Two-Component Regulation of Quorum Sensing and Secondary Metabolite Production in BacteriaHost-associated bacteria, whether pathogenic or beneficial, survive in an environment determined by the host and its associated microbial community. Host-associated bacteria use sensory networks to regulate the expression of secondary metabolites needed to establish and maintain host associations. Phenazines are secondary metabolites important in plant disease control by Pseudomonas aureofaciens and also in virulence by the human pathogen P. aeruginosa. In both bacteria, phenazines are regulated, in part, by a two-component quorum sensing (QS) system (e.g. phenazines are expressed only after bacterial populations reach a sufficient density or quorum). A novel two-component regulatory system (RpeA/RpeB) was identified in both bacteria that, when mutated, removed the requirement for QS and resulted in overproduction of phenazines. This finding is particularly interesting because mutations in the (RpeA/RpeB) system, which bypasses QS control, could severely limit the effectiveness of new antibiotic therapies aimed at reducing bacterial virulence and infection by interfering with QS regulation. This proposal outlines a systematic approach to characterize the novel negative two component regulatory system (RpeA/RpeB) and its linkage to nutritional sensing and QS. The linkage between these two sensory systems will be determined in both P. aureofaciens and P. aeruginosa using global gene expression analysis. The effect of loss of this two-component system on the ecological fitness of the bacteria when associated with hosts also will be determined. Understanding how loss of this two-component system bypasses QS regulation will provide insights into strategies for enhancing secondary metabolite production essential for successful plant disease control or for blocking secondary metabolite production required for human disease establishment. The multidisciplinary nature of the proposed research will i) provide training opportunities for undergraduate and graduate students and integration of information and technologies into lectures, laboratory exercises and existing undergraduate and graduate research opportunities, ii) outreach via the American Phytopathological Society Education Center.

B.Pierson IIIPROPOSAL#NSF 0545804TITLE：细菌群体感应和次生代谢物产生的新的双组分调节宿主相关细菌，无论是致病的还是有益的，都在宿主及其相关微生物群落决定的环境中生存。寄主相关细菌使用感觉网络来调节建立和维持寄主关联所需的次生代谢物的表达。吩嗪类化合物是由金黄色假单胞菌控制植物病害的重要次生代谢产物，也是人类病原菌铜绿假单胞菌致病的重要物质。在这两种细菌中，吩嗪类药物在一定程度上受到双组分群体感应(QS)系统的调节(例如，吩嗪类药物只有在细菌数量达到足够的密度或法定数量后才表达)。在这两种细菌中都发现了一种新的双组分调控系统(RpeA/RpeB)，当突变时，该系统消除了对QS的要求，并导致吩嗪类药物的过量生产。这一发现特别有趣，因为绕过QS控制的(RpeA/RpeB)系统的突变可能会严重限制新的抗生素疗法的有效性，这些疗法旨在通过干扰QS调节来降低细菌的毒力和感染。这项提案概述了一种系统的方法来描述新的负两组分调控系统(RpeA/RpeB)及其与营养感知和质量保证的联系。在金黄色葡萄球菌和铜绿假单胞菌中，这两个感觉系统之间的联系将通过全球基因表达分析来确定。失去这种双组分系统对细菌与宿主结合时的生态适宜性的影响也将得到确定。了解这一双组分系统的损失如何绕过QS调节，将为提高次生代谢物产生的战略提供洞察，这对成功的植物病害控制至关重要，或阻止人类疾病建立所需的次生代谢物产生。拟议研究的多学科性质将：i)为本科生和研究生提供培训机会，并将信息和技术整合到讲座、实验室练习和现有的本科生和研究生研究机会中；ii)通过美国植物病理学学会教育中心进行推广。