The pel exopolysaccharide gene cluster of Pseudomonas aeruginosa

摘要 铜绿假单胞菌感染导致人群显著发病率和死亡率 患有囊性纤维化(CF)。这些感染的一个关键特征是它们涉及生物被膜。 社区。几种关键生物膜基质成分(如PEL、PSL)的表达 胞外多糖和基质粘附素CDRA)在相互作用时被启动 有表面的。在铜绿假单胞菌中有两种已知的表面传感系统，WSP和PIL。 CHP，两者都通过刺激细胞内信号c-di-GMP的产生而起作用。整体而言 这项应用的目标是研究WSP表面传感系统，它的信号 回应，它如何将表面传感与其他表面传感系统Pil-CHP相结合 在生物膜聚集体组装的早期阶段。我们还将检查致病原 不同表面感觉基因在小鼠感染和感染模型中的适应度优势 体外细胞免疫学检测。这项提议将弥补我们在如何 表面传感的工作原理及其在发病机制中的贡献。未来的治疗策略 (特别是针对生物膜社区的)将从这种知识中受益。

Abstract Pseudomonas aeruginosa infections result in significant morbidity and mortality in people suffering from cystic fibrosis (CF). A key feature of these infections is that they involve biofilm communities. The expression of several key biofilm matrix components (e.g. the Pel,Psl exopolysaccharides and the matrix adhesin CdrA) are known to be initiated upon interaction with a surface. There are two known surface sensing systems in P. aeruginosa, Wsp and Pil- Chp, that both act by stimulating production of the intracellular signal c-di-GMP. The overall goals of this application are to investigate the Wsp surface sensing system, the signals it responds to, how it integrates surface sensing with the other surface sensing system Pil-Chp during the early stages of biofilm aggregate assembly. We will also examine the pathogenic fitness advantages of different surface sensing genotypes in murine models of infection and in vitro cellular immunological assays. This proposal will address gaps in our knowledge as to how surface sensing works and its contribution to pathogenesis. Future therapeutic strategies (particularly ones directed towards biofilm communities) will benefit from such knowledge.