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，可引起慢性肺部感染，与囊性纤维化（CF）和免疫功能低下患者（包括慢性伤口患者）气道中的生物膜形成有关。生物膜是包裹在基质内的微生物结构群落，对抗菌剂和宿主防御具有抗性。目前尚不清楚生物膜细菌如何在CF气道内存活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，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在铜绿假单胞菌生物膜结构完整性和对抗菌剂和宿主防御的耐受性中的作用。目的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，并定义其作用

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.