The pel exopolysaccharide gene cluster of Pseudomonas aeruginosa

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能够形成称为生物膜的表面相关群落。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）患者气道中的慢性感染。生物膜细菌产生一种或多种细胞外聚合物质（EPS），作为支架，将生物膜细胞聚集在一起并固定在表面。一段时间以来，海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，藻酸盐不是非黏液菌株EPS基质的重要组成部分，而非黏液菌株是大多数机会性生物膜感染的原因，也是CF患者的第一个定植。相反，似乎有其他EPS成分介导生物膜的形成。我们的实验室和其他研究人员发现，铜绿假单胞菌具有编码两种替代多糖的能力，称为Psl和Pel，它们在细胞表面相互作用和生物膜形成中起着关键作用。本提案的重点是Pel基因簇。我们的总体目标是确定Pel在生物膜发育、结构、抗微生物药物耐药性和发病机制中的作用。进一步了解这一关键的生物膜成分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了解仍然存在差距。我们发现了一种新的EPS位点，它是铜绿假单胞菌生物膜形成所必需的。由于基质为生物膜的发育提供了关键的保护作用和支架，旨在破坏基质的药物将具有治疗价值。对Pel的深入分析可能会导致此类药物的开发，并改善C型患者以及其他铜绿假单胞菌感染涉及生物膜的个体的生活质量。公共卫生相关性：该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制中的作用。将探讨Pel在多糖生产、生物膜形成和发病机制中的作用。

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.