Regulation of biofilm formation and pathogenesis in Bordetella pertussis

 描述（由申请方提供）：革兰氏阴性菌百日咳杆菌是一种人类限制性病原体，可引起严重呼吸道感染和百日咳或百日咳。最近B的上升。美国和其它高收入国家的百日咳感染和该疾病，沿着对当前商业百日咳疫苗的免疫力减弱，需要研究了解该细菌所采用的致病机制。我们的总体假设是，生物膜的形成是必不可少的持久定植的呼吸道和发病机制的B。百日咳。控制主要是动物病原体B的生物膜发展。支气管败血症是由BpsR介导的，BpsR是一种高度保守的转录调节因子。此外，BpsR双重激活或抑制大量基因的表达，这些基因在毒力、转录调节、代谢和其他细胞过程中发挥作用。关于BpsR在B中的作用还不清楚。百日咳。BpsR在B中的功能研究由于不能构建缺乏bpsR基因的突变株，百日咳的研究受到阻碍。这表明bpsR是B的一个必需基因。百日咳。我们推测BpsR通过调节参与基本代谢途径、发病机制和生物膜形成的基因的表达，控制B的能力。百日咳在呼吸道中存活。在具体目标1中，我们将利用四环素依赖性条件沉默系统来研究其在实验室生长，基因表达和生物膜发育中的作用。在特定目的2中，这些研究将扩展至B的鼻内小鼠模型。百日咳感染和生物膜发育，以确定其在呼吸器官上的生物膜的定殖和形成中的作用。

 DESCRIPTION (provided by applicant): The Gram-negative bacterium Bordetella pertussis is a human restricted pathogen that causes severe respiratory infection and the disease known as whooping cough or pertussis. The recent rise in B. pertussis infections and the disease in the USA and other high income countries, along with waning immunity to current commercial pertussis vaccines necessitate research on understanding the pathogenic mechanisms employed by this bacterium. Our overall hypothesis is that the formation of biofilms is essential for persistent colonization of the respiratory tract and pathogenesis of B. pertussis. Control of biofilm development in the largely animal pathogen B. bronchiseptica is mediated by BpsR, a highly conserved transcriptional regulator. Additionally, BpsR dually activates or represses the expression of a large number of genes which have roles in virulence, transcriptional regulation, metabolic and other cellular processes. Nothing is known about the role of BpsR in B. pertussis. Functional studies of BpsR in B. pertussis have been hindered by the inability to construct a mutant strain lacking the bpsR gene. This suggests that bpsR is an essential gene in B. pertussis. We hypothesize that by regulating the expression of genes involved in essential metabolic pathways, pathogenesis and biofilm formation, BpsR controls the ability of B. pertussis to survive in the respiratory tract. In Specific Aim 1, we will utilize a tetracycline dependent conditional silencing system to examine its role in laboratory growth, gene expression and biofilm development. In Specific Aim 2, these studies will be extended to an intranasal mouse model of B. pertussis infection and biofilm development to identify its role in colonization of and formation of biofilms on respiratory organs.