The pel exopolysaccharide gene cluster of Pseudomonas aeruginosa

铜绿假单胞菌胞外多糖基因簇

• 批准号: 10376298
• 负责人: MATTHEW R. PARSEK
• 金额: $ 45.71万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-17 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10376298
• 关键词: Address; Bacteria; Bacterial Adhesins; Cells; Chronic; Clinical; Coculture Techniques; Communities; Cystic Fibrosis; Data; Elements; Environmental Risk Factor; Event; Future; Gene Cluster; Genotype; Goals; Growth; Human; Immunology procedure; In Vitro; Infection; Knowledge; Lead; Link; Membrane; Microbial Biofilms; Morbidity - disease rate; Mus; Mutagenesis; Mutation; Natural Immunity; Pathogenesis; Pathogenicity; Persons; Predisposition; Production; Proteins; Pseudomonas aeruginosa; Pseudomonas aeruginosa infection; Role; Signal Transduction; Stimulus; Stress; Structure; Surface; Surveys; Swimming; System; Testing; Therapeutic; Ursidae Family; Work; Wound models; antimicrobial; cell envelope; chronic infection; experimental study; fitness; genetic approach; mortality; mouse model; mutant; neutrophil; sensor; transposon sequencing

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.

抽象的 铜绿假单胞菌感染导致人们显着发病和死亡率 患有囊性纤维化（CF）。这些感染的关键特征是它们涉及生物膜 社区。几个关键生物膜基质组件的表达（例如PEL，PSL 已知在相互作用时启动外多糖和基质粘附素CDRA） 表面。铜绿假单胞菌，WSP和PIL-有两个已知的表面传感系统 CHP，两者都通过刺激细胞内信号C-DI-GMP的产生来起作用。总体 该应用的目标是调查WSP表面传感系统 响应，它如何将表面传感与其他表面传感系统PIL-CHP整合在一起 在生物膜聚集体的早期阶段。我们还将检查致病性 在感染的鼠模型中，不同表面传感基因型的适应性优势和 体外细胞免疫学测定。该建议将解决我们知识的差距 表面传感作品及其对发病机理的贡献。未来的治疗策略 （尤其是针对生物膜社区的人）将从这种知识中受益。