The pel exopolysaccharide gene cluster of Pseudomonas aeruginosa

铜绿假单胞菌胞外多糖基因簇

• 批准号: 7893711
• 负责人: MATTHEW R. PARSEK
• 金额: $ 50.24万
• 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 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7893711
• 关键词: Alginates; Antimicrobial Resistance; Bacteria; Biocide; Biological; Biological Assay; Carbohydrates; Cell surface; Cells; Chronic; Communities; Cystic Fibrosis; Data; Defect; Development; Gene Cluster; Genes; In Vitro; Individual; Infection; Insertion Mutation; Knowledge; Lead; Maps; Mediating; Medical Device; Microbial Biofilms; Modeling; Molecular; Mus; Mutagenesis; Nature; Operon; Pathogenesis; Patients; Phenotype; Play; Polysaccharides; Primer Extension; Production; Proteins; Pseudomonas aeruginosa; Quality of life; Race; Role; Series; Structure; Surface; Testing; Therapeutic; Time; antimicrobial drug; cystic fibrosis patients; extracellular; improved; insight; monomer; mutant; novel; promoter; public health relevance; research study; response; scaffold

DESCRIPTION (provided by applicant): An important feature of Pseudomonas aeruginosa pathogenesis is the ability to form surface- associated communities called biofilms. Several types of P. aeruginosa infections are characterized by biofilm formation, including the colonization of indwelling medical devices and the chronic infections present in the airways of people suffering from cystic fibrosis (CF). Biofilm bacteria produce one or more extracellular polymeric substances (EPS) that act as a scaffold, holding biofilm cells together and to a surface. For some time, alginate has been considered the major polysaccharide of the P. aeruginosa EPS biofilm matrix. Recently, our studies indicate that alginate is not a significant component of the EPS matrix of nonmucoid strains, which are responsible for most opportunistic biofilm infections and are also the first to colonize CF patients. Instead, there appear to be other EPS components that mediate biofilm formation. Our lab and others discovered that P. aeruginosa has the capacity to encode two alternative polysaccharides, designated Psl and Pel, which play critical roles in cell surface interactions and biofilm formation. The focus of this proposal is the Pel gene cluster. Our overall objective is to determine the role of Pel in biofilm development, structure, resistance to antimicrobial agents, and pathogenesis. A further understanding of this critical biofilm component will lead to strategies aimed at inhibiting biofilm formation, a key aspect of P. aeruginosa pathogenesis. Despite significant advancements in our knowledge of P. aeruginosa biofilm development, there remain gaps in our understanding of the biofilm matrix composition, as well as the genes responsible for producing this matrix. We have discovered a novel EPS locus that is essential for formation of P. aeruginosa biofilms. Since the matrix provides a critical protective role as well as a scaffold for the developing biofilm, agents aimed at disrupting the matrix would have therapeutic value. A thorough analysis of Pel may lead to the development of such agents and improve the quality of life for C patients as well as individuals with other P. aeruginosa infections that involve biofilms. PUBLIC HEALTH RELEVANCE: is proposal is focused on examining the role of the important biofilm exopolysaccharide Pel in Pseudomonas aeruginosa biofilm formation and pathogenesis. The role of Pel in polysaccharide production, biofilm formation and pathogenesis will be explored.

描述（由申请人提供）：铜绿假单胞菌发病机制的一个重要特征是形成称为生物膜的表面相关群落的能力。几种类型的铜绿假单胞菌感染以生物膜形成为特征，包括留置医疗器械的定植和囊性纤维化 (CF) 患者气道中存在的慢性感染。生物膜细菌产生一种或多种细胞外聚合物 (EPS)，充当支架，将生物膜细胞固定在一起并固定在表面上。一段时间以来，海藻酸盐被认为是铜绿假单胞菌 EPS 生物膜基质的主要多糖。最近，我们的研究表明，海藻酸盐不是非粘液菌株 EPS 基质的重要组成部分，非粘液菌株是大多数机会性生物膜感染的原因，也是第一个在 CF 患者中定植的菌株。相反，似乎还有其他 EPS 成分介导生物膜形成。我们的实验室和其他人发现铜绿假单胞菌能够编码两种替代多糖，称为 Psl 和 Pel，它们在细胞表面相互作用和生物膜形成中发挥着关键作用。该提案的重点是Pel基因簇。我们的总体目标是确定 Pel 在生物膜发育、结构、抗菌药物耐药性和发病机制中的作用。对这一关键生物膜成分的进一步了解将有助于制定旨在抑制生物膜形成的策略，生物膜形成是铜绿假单胞菌发病机制的一个关键方面。尽管我们对铜绿假单胞菌生物膜发育的了解取得了重大进展，但我们对生物膜基质组成以及负责产生这种基质的基因的理解仍然存在差距。我们发现了一个新的 EPS 基因座，它对于铜绿假单胞菌生物膜的形成至关重要。由于基质提供了关键的保护作用以及正在发育的生物膜的支架，因此旨在破坏基质的药剂将具有治疗价值。对 Pel 的彻底分析可能会导致此类药物的开发，并改善 C 患者以及涉及生物膜的其他铜绿假单胞菌感染个体的生活质量。公共健康相关性：该提案的重点是研究重要的生物膜胞外多糖 Pel 在铜绿假单胞菌生物膜形成和发病机制中的作用。将探讨 Pel 在多糖产生、生物膜形成和发病机制中的作用。