The pel exopolysaccharide gene cluster of Pseudomonas aeruginosa

铜绿假单胞菌胞外多糖基因簇

• 批准号: 10609450
• 负责人: MATTHEW R. PARSEK
• 金额: $ 45.48万
• 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/10609450
• 关键词: 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; 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; 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.

摘要 铜绿假单胞菌感染导致人的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膜 社区.几种关键的生物膜基质组分（例如Pel、Psl）的表达 已知胞外多糖和基质粘附素CdrA）在相互作用后启动 有一个表面。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的产生起作用。整体 本应用程序的目标是研究Wsp表面传感系统及其信号 它如何将表面传感与其他表面传感系统Pil-Chp集成 在生物膜聚集体组装的早期阶段。我们还将检查病原体 不同表面传感基因型在感染小鼠模型和感染中的适应性优势 体外细胞免疫测定。这项建议将填补我们在以下方面的知识空白： 表面传感工作及其对发病机制的贡献。未来的治疗策略 （特别是针对生物膜群落的那些）将受益于这样的知识。