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理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的特征是生物膜形成，包括留置医疗装置的定殖以及患有囊性纤维化（CF）的呼吸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物质（EP），可充当支架，将生物膜细胞固定在一起和表面。一段时间以来，藻酸盐一直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，藻酸盐并不是非糖类菌株的EPS基质的重要组成部分，这些组件是导致大多数机会性生物膜感染的原因，也是第一个定殖CF患者的人。取而代之的是，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，铜绿假单胞菌有能力编码指定为PSL和PEL的两种替代多糖，它们在细胞表面相互作用和生物膜形成中起关键作用。该建议的重点是PEL基因簇。我们的总体目标是确定PEL在生物膜发育，结构，对抗菌剂的抗性和发病机理中的作用。对这种关键生物膜成分的进一步了解将导致旨在抑制生物膜形成的策略，这是铜绿假单胞菌发病机理的关键方面。尽管我们对铜绿假单胞菌生物膜发育的了解有了显着进步，但我们对生物膜基质组成以及负责产生该基质的基因仍然存在差距。我们发现了一个新型的EPS基因座，这对于形成铜绿假单胞菌生物膜至关重要。由于矩阵提供了关键的保护作用以及开发生物膜的脚手架，因此旨在破坏矩阵的代理具有治疗价值。对PEL进行彻底的分析可能会导致这种药物的发展，并改善C患者以及患有涉及生物膜的其他铜绿假单胞菌感染的患者的生活质量。公共卫生相关性：IS提案的重点是研究重要的生物膜外多糖PEL在铜绿假单胞菌生物膜形成和发病机理中的作用。将探索PEL在多糖产生，生物膜形成和发病机理中的作用。