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Pseudomonas biofilms and immunity

假单胞菌生物膜和免疫

基本信息

批准号：
9188512
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 2018-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9188512
关键词：
Adhesions Alginates Alpha Cell Antimicrobial Resistance Bacteria Biochemical Cell Communication Cell surface Cells Chronic Clinical Communities Cystic Fibrosis Development Event Exhibits Goals Growth 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 Pulmonary Fibrosis Research Resistance Resolution Role Signal Transduction Signal Transduction Pathway Signaling Molecule Source Structure Structure-Activity Relationship Surface Testing Therapeutic Time Translating antimicrobial antimicrobial drug chronic wound cystic fibrosis airway cystic fibrosis patients experimental study extracellular feeding human disease insight member microbial community mortality mucoid neutrophil novel pathogen public health relevance 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，可引起与囊性纤维化 (CF) 和免疫功能低下患者（包括慢性伤口患者）气道中生物膜形成相关的慢性肺部感染。生物膜是包裹在基质内的结构化微生物群落，表现出对抗菌药物和宿主防御的抵抗力。目前尚不清楚生物膜细菌如何在 CF 气道内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。本应用的重点是铜绿假单胞菌生物膜基质的两个关键成分，即细胞外多糖 Psl 和蛋白质粘附 CdrA。我们的总体目标是确定 Psl 和 CdrA 在生物膜结构完整性以及铜绿假单胞菌对抗菌药物和宿主防御的耐受性中的作用。目标 1 将重点研究铜绿假单胞菌生物膜基质完整性所需的结构-功能关系，并定义生物膜基质成分调节铜绿假单胞菌与人类吞噬细胞的相互作用。在第二个目标中，我们将定义一种新的信号转导途径，负责 Psl 依赖性信号传导的前馈机制。即使存在强大的免疫反应，我们对铜绿假单胞菌如何在 CF 气道中生存的理解仍然存在重大差距。由于生物膜基质具有保护作用，旨在了解基质成分功能的研究将为 CF 发病机制和其他铜绿假单胞菌感染（其中生物膜与人类疾病相关）的早期事件提供见解和治疗策略。