Pseudomonas biofilms and persistence

描述(申请人提供)：生物膜，定义为附着在表面的微生物群落，与许多人类细菌病原体的慢性疾病有关。条件致病菌铜绿假单胞菌在囊性纤维化患者的肺、耳粘膜和尿路上皮细胞或导尿管等多种表面形成生物膜。虽然关于铜绿假单胞菌生物膜体外发育的分子生物学和遗传学有相当多的信息，但对这种机会致病菌如何在体内建立感染导致生物被膜和持久性的了解很少。这些知识差距的部分原因是缺乏合适的模型来研究生物膜生长的铜绿假单胞菌。这项提案的总体目标是开发一个模型系统，用于评估铜绿假单胞菌的致病机理和与生物被膜相关的持续性疾病期间的宿主反应。在目标1中，将建立龙猫中耳感染模型。目标2中的实验将确定在体外促进生物膜形成和持久性的细菌因素是否也与龙猫中耳感染模型的疾病进展有关。 尽管我们对铜绿假单胞菌生物被膜体外发育的了解有了很大的进步，但我们对这些发现在体内的相关性的理解仍然存在差距。这是由于缺乏合适的模型来研究铜绿假单胞菌的慢性和持续性致病机制。这种模型的发展可能会导致更好地了解宿主-病原体的界面，并导致改善涉及生物被膜的铜绿假单胞菌感染患者的生活质量的策略。此外，我们的长期计划是将该项目作为针对NIH NIAID或NHLBI的项目应用程序的基础，以调查持续感染中的宿主-病原体界面。 生物膜被定义为附着在表面的微生物群落，与许多人类细菌病原体的慢性疾病有关。铜绿假单胞菌在多种表面形成生物膜，包括囊性纤维化患者的肺、耳表面粘膜和尿路上皮细胞或导尿管。这项应用旨在开发一种模型系统，用于研究铜绿假单胞菌在与生物被膜相关的持续性疾病期间的发病机制和宿主反应。这种模型的发展将导致更好地了解宿主-病原体的界面，并导致改善涉及生物被膜的铜绿假单胞菌感染患者的生活质量的策略。

DESCRIPTION (provided by applicant): Biofilms, which are defined as communities of microorganisms attached to a surface, are associated with chronic diseases of many human bacterial pathogens. The opportunistic pathogen Pseudomonas aeruginosa forms biofilms on a variety of surfaces including the lungs of cystic fibrosis patients, the mucosa of ear surfaces, and epithelial cells or catheters of the urinary tract. While there is a considerable amount of information regarding the molecular biology and genetics of P. aeruginosa biofilm development in vitro, little is known about how this opportunistic pathogen establishes infections that lead to biofilms and persistence in vivo. These knowledge gaps are due, in part, to the lack of suitable models for investigating biofilm-grown P. aeruginosa. The overall objective of this proposal is to develop a model system for evaluating P. aeruginosa pathogenesis and the host response during persistent diseases associated with biofilms. In aim 1, a chinchilla middle ear infection model will be developed. Experiments in aim 2 will determine if bacterial factors that contribute to biofilm formation and persistence in vitro are also associated with disease progression in the chinchilla middle ear infection model. Despite significant advancements in our knowledge of P. aeruginosa biofilm development in vitro, there remain gaps in our understanding of the in vivo relevance of such findings. This is due to the lack of suitable models for investigating the chronic and persistent aspects of P. aeruginosa pathogenesis. Development of such models may lead to a better understanding of the host-pathogen interface and lead to strategies to improve the quality of life for patients with P. aeruginosa infections that involve biofilms. Moreover, our long-range plan is for this project to serve as a foundation for a program project application targeted to NIH NIAID or NHLBI to investigate the host-pathogen interface in persistent infections. Biofilms, which are defined as communities of microorganisms attached to a surface, are associated with chronic diseases of many human bacterial pathogens. Pseudomonas aeruginosa forms biofilms on a variety of surfaces including the lungs of cystic fibrosis patients, the mucosa of ear surfaces, and epithelial cells or catheters of the urinary tract. This application seeks to develop a model system for studying P. aeruginosa pathogenesis and the host response during persistent diseases associated with biofilms. Development of such a model will lead to a better understanding of the host-pathogen interface and lead to strategies that improve the quality of life for patients with P. aeruginosa infections that involve biofilms.