Pseudomonas biofilms and immunity

假单胞菌生物膜和免疫

基本信息

批准号：
8978289
负责人：
Daniel J Wozniak
金额：
$ 38.54万
依托单位：
OHIO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-01-01 至 2017-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8978289
关键词：
Adhesions Alginates Antimicrobial Resistance Bacteria Biochemical Cell Communication Cell surface Cells Chronic Clinical Communities Cystic Fibrosis Development Event Exhibits Extracellular Matrix Goals Growth Health Hereditary Disease Host Defense Human Immune Immune response Immunity Individual Infection Inflammatory Response Link Lung Mediating Microbe Microbial Biofilms Microscopy Morbidity - disease rate Pathogenesis Patients Phagocytes Polysaccharides Prevalence Property Proteins Pseudomonas Pseudomonas aeruginosa Research Resistance Resolution Role Signal Transduction Signal Transduction Pathway Signaling Molecule Source Structure Structure-Activity Relationship Surface Testing Therapeutic Time Translating antimicrobial antimicrobial drug base chronic wound cystic fibrosis airway cystic fibrosis patients feeding human disease insight intercellular communication member microbial community mortality mucoid neutrophil novel pathogen research study resistance mechanism sugar

项目摘要

DESCRIPTION (provided by applicant): Pseudomonas aeruginosa is an opportunistic bacterial pathogen that causes chronic lung infections associated with biofilm formation in the airways of cystic fibrosis (CF) and immune-compromised patients, including those with chronic wounds. Biofilms are structured communities of microbes encased within a matrix and exhibit resistance to antimicrobials and host defenses. It remains unclear how biofilm bacteria survive within the CF airways or the interplay of P. aeruginosa matrix materials with host immune cells. The focus of this application is on two critical components of the P. aeruginosa biofilm matrix biofilm matrix, an extracellular polysaccharide Psl and a protein adhesion CdrA. Our overall objective is to determine the roles of Psl and CdrA in biofilm structural integrity and tolerance o P. aeruginosa to antimicrobials and host defense. Aim 1 will focus investigating structure- function relationships necessary for P. aeruginosa biofilm matrix integrity and define the roles of biofilm matrix components in modulating interactions of P. aeruginosa with human phagocytic cells. In the second aim we will define a novel signal transduction pathway responsible for a feed-forward mechanism of Psl-dependent signaling. There remain significant gaps in our understanding of how P. aeruginosa survive in the CF airway even in the presence of a robust immune response. Since the biofilm matrix provides a protective role, studies aimed at understanding the functions of matrix components will provide insights and therapeutic strategies aimed at early events of CF pathogenesis and other P. aeruginosa infections where biofilms are linked with human disease.

描述（由申请人提供）：铜绿假单胞菌是一种机会性细菌病原体，会引起与囊性纤维化（CF）气道中与生物膜形成相关的慢性肺部感染和免疫强化患者，包括患有慢性伤口的患者。生物膜是包裹在基质中的微生物的结构化群落，并表现出对抗菌和宿主防御的抗性。目前尚不清楚生物膜细菌如何在CF气道中生存或铜绿假单胞菌基质材料与宿主免疫细胞的相互作用。该应用的重点是铜绿假单胞菌生物膜基质生物膜基质，细胞外多糖PSL和蛋白质粘附CDRA的两个关键成分。我们的总体目的是确定PSL和CDRA在生物膜结构完整性和耐受性O铜绿对抗菌和宿主防御中的作用。 AIM 1将集中研究结构 - 铜绿假单胞菌生物膜矩阵完整性所必需的结构 - 功能关系，并定义在调节铜绿假单胞菌与人吞噬细胞的相互作用时，生物膜基质成分。在第二个目标中，我们将定义一个新型的信号转导途径，负责PSL依赖性信号传导的前进机理。即使存在强大的免疫反应，我们对铜绿假单胞菌如何在CF气道中如何存活的理解仍然存在很大的差距。由于生物膜矩阵提供了保护作用，因此旨在了解基质组件功能的研究将提供针对CF发病机理和其他铜绿假单胞菌感染的早期事件的见解和治疗策略，其中生物膜与人类疾病有关。