Pseudomonas biofilms and immunity

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，可导致囊性纤维化(CF)患者和免疫功能低下患者(包括慢性伤口患者)的呼吸道生物膜形成相关的慢性肺部感染。生物膜是包裹在基质中的结构化微生物群落，对抗菌剂和宿主防御具有抵抗力。目前尚不清楚生物膜细菌如何在CF呼吸道内生存，也不清楚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生物膜基质的两个关键成分，即胞外多糖PSL和蛋白粘附性CDRA。我们的总体目标是确定PSL和CDRA在铜绿假单胞菌生物膜结构完整性、对抗生素的耐受性和宿主防御中的作用。目标1将重点研究铜绿假单胞菌生物膜基质完整性所必需的结构-功能关系，并确定 调节铜绿假单胞菌与人吞噬细胞相互作用的生物膜基质成分。在第二个目标中，我们将定义一个新的信号转导通路，负责PSL依赖信号的前馈机制。在我们对铜绿假单胞菌如何在CF气道中生存的理解上仍然存在着显著的差距，即使在存在强大的免疫反应的情况下也是如此。由于生物膜基质提供了保护作用，旨在了解基质成分功能的研究将提供针对CF发病机制和其他生物膜与人类疾病相关的铜绿假单胞菌感染的早期事件的见解和治疗策略。

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.