Quorum Sensing in Burkolderia mallei: an antivirulence therapeutic

细菌群体感应涉及小分子细胞-细胞信号传递，允许协调行为 在种群中的单个细胞之间。NIAID B类优先病原体的群体感应 伯克霍尔德里亚·马雷对此特别感兴趣。首先，像某些其他病原体一样，如假单胞菌 铜绿假单胞菌群体感应参与了马来芽胞杆菌的毒力。努力开发抗假单胞菌药物 由于缺乏合适的假单胞菌动物模型，群体感应抑制剂受到阻碍 感染。B.Mallei的这些模型的可用性使我们能够启动一个计划， 最终将导致在动物模型中测试小分子抑制剂的有效性。第二，一个共同的 致力于群体感应的科学家认为，它允许病原体(或至少是共生菌) 区分寄主和自由生活状态，伯克霍尔德氏菌是一种专性动物病原体，具有 没有已知的环境水库。法定人数检测必须涉及不同阶段的区分或 这种病原体的感染类型。最后，最明显的是，B.Mallei中的群体感应是 反S马来疗法的发展。格林伯格博士建议调整他最近制定的法定人数 用于高通量筛选抑制剂的传感报告系统。将进行更多的实验 在确定法定人数控制的FI时。马来基因。这些实验将涉及启动子陷阱。 技术，并要求构建一个群体感应规则的“去内脏的马利氏杆菌和或 密切相关的FI。泰兰人。提出了一种新的插入基因失活反选择方法。 将描述泰兰人，以及将该程序扩展到B.meillei的计划。这种生成的方法 B.Mallei组成员的突变代表着一项重大进步，它将克服目前的 FI面临的障碍。马雷生物学家。

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.