Quorum Sensing in Burkolderia mallei: an antivirulence therapeutic

鼻疽伯克氏菌的群体感应：一种抗毒疗法

• 批准号: 8236992
• 负责人: Everett P Greenberg
• 金额: $ 30.59万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8236992
• 关键词: Animal Model; Animals; Anti-Infective Agents; Bacteria; Behavior; Belief; Burkholderia mallei; Categories; Cells; Centers of Research Excellence; Development; Discrimination; Elements; Emerging Communicable Diseases; Genes; Genetic; Individual; Infection; Investigation; Laboratories; Lead; Life; Light; Malleus; Methods; Modeling; Motion; Mutation; National Institute of Allergy and Infectious Disease; Nature; Population; Procedures; Pseudomonas; Pseudomonas aeruginosa; Recruitment Activity; Regulation; Regulon; Reporter; Research; Role; Scientist; Signal Transduction; Staging; System; Techniques; Technology; Testing; Therapeutic; Therapeutic Agents; Virulence; Virulence Factors; Work; biodefense; efficacy testing; high throughput screening; inhibitor/antagonist; interest; knowledge base; member; pathogen; programs; promoter; quorum sensing; receptor; research study; small molecule; therapeutic development; tool

Bacterial quorum sensing involves small molecule cell-cell siganling that allows coordination of behavior among individual cells in a population. Quorum sensing in the NIAID Category B Priority Pathogen Burkholderia mallei holds a particular interest. First, like for certain other pathogens such as Pseudomonas aeruginosa quorum sensing is involved in virulence of B. mallei. Efforts to develop anti-Pseudomonas quorum sensing inhibitors have been hindered by the lack of adequate animal models for Pseud0monas infections. The availability of such models for B. mallei affords us the ability to put a program in motion that will eventually lead to tests of efficacy for small molecule inhibitors in animal models. Second, a common belief among scientists working on quorum sensing is that it allows a pathogen (or at least a symbiont) to discriminate between a host and a free-living state, Burkholderia mallei is an obligate animal pathogen with no known environmental reservoir. Quorum sensing must be involved in discrimination of different stages or types of infections by this pathogen. Finally, a most obviously, quorum sensing in B. Mallei is a target for anti-S. mallei therapeutic development. Dr. Greenberg proposes to adapt his recently developed quorum sensing reporter system for use in a high-throughput screen for inhibitors. Further experiments will be aimed at identification of quorum-controlled fi. mallei genes. These experiments will involve promoter-trap technology and require the construction of a quorum-sensing regular "gutted strain of B. mallei and or the closely related fi. thailandensis. A new counter-selection method for insertional gene inactiviation in B. thailandensis will be described, as will plans to extend the procedure to B. meillei. This method for generating mutations in members of the B. mallei group represents a major advance that will overcome a current obstacle faced by fi. mallei biologists.

细菌群体传感涉及小分子细胞 - 细胞siganling，允许行为协调 在人群中的单个细胞中。 niAID类别B优先病原体中的法定感应 Burkholderia Mallei具有特别的利益。首先，就像某些其他病原体（如假单胞菌）一样 铜绿群群传感与麦芽芽孢杆菌的毒力有关。努力发展抗假单胞菌 缺乏适当的动物模型来阻碍群体传感抑制剂 感染。此类模型为B. Mallei提供的可用性使我们能够将计划进行运动 最终将导致动物模型中小分子抑制剂的功效测试。第二，一个常见 从事法定人数感应的科学家之间的信念是，它允许病原体（或至少共生） Burkholderia Mallei区分宿主和自由生活状态，是一种强制性动物病原体 没有已知的环境水库。法定感应必须参与不同阶段的歧视或 这种病原体的感染类型。最后，最明显的是，Mallei中的法定人数是 抗S。 Mallei治疗发展。格林伯格博士提议适应他最近开发的法定人数 在高通量屏幕中使用的传感记者系统用于抑制剂。将进一步实验 识别法定人数控制的FI。马利基因。这些实验将涉及启动子陷阱 技术，需要构建法定感应的常规“肠杆菌菌株，或 密切相关的FI。泰国人。一种用于插入基因灭活的新的反选择方法。 将描述泰国人，并计划将程序扩展到B. Meil​​lei。此方法生成 B. mallei组成员的突变代表了一个重大进展，将克服当前 FI面临的障碍。马利生物学家。