Pseudomonas biofilms and persistence

描述（由申请人提供）：生物膜定义为附着在表面上的微生物群落，与许多人类细菌病原体的慢性疾病相关。条件致病菌铜绿假单胞菌在多种表面上形成生物膜，包括囊性纤维化患者的肺、耳表面的粘膜和尿道的上皮细胞或导管。虽然有相当数量的信息有关铜绿假单胞菌生物膜体外发展的分子生物学和遗传学，很少有人知道这种机会致病菌如何建立感染，导致生物膜和持久性在体内。这些知识差距部分是由于缺乏合适的模型来研究生物膜生长的铜绿假单胞菌。本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发病机制和与生物膜相关的持续性疾病期间的宿主反应。目的一：建立灰鼠中耳感染模型。目标2中的实验将确定有助于生物膜形成和体外持久性的细菌因素是否也与灰鼠中耳感染模型中的疾病进展相关。 尽管我们对铜绿假单胞菌生物膜体外形成的认识有了显著的进步，但我们对这些发现的体内相关性的理解仍存在差距。这是由于缺乏合适的模型来研究铜绿假单胞菌发病机制的慢性和持续性方面。这种模型的发展可能会导致宿主-病原体界面的更好的理解，并导致策略，以改善患者的生活质量与铜绿假单胞菌感染，涉及生物膜。此外，我们的长期计划是将该项目作为针对NIH NIAID或NHLBI的项目应用的基础，以调查持续感染中的宿主-病原体界面。 生物膜是附着在物体表面的微生物群落，与许多人类细菌性病原体的慢性疾病有关。铜绿假单胞菌在多种表面上形成生物膜，包括囊性纤维化患者的肺、耳表面的粘膜和尿道的上皮细胞或导管。本申请寻求开发用于研究铜绿假单胞菌发病机理和与生物膜相关的持续性疾病期间的宿主反应的模型系统。这种模型的开发将导致更好地理解宿主-病原体界面，并导致改善涉及生物膜的铜绿假单胞菌感染患者生活质量的策略。

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.