Impact of mucin fermenting microbes on the virulence of Pseudomonas aeruginosa in chronic rhinosinusitis

标题：粘蛋白发酵微生物对铜绿假单胞菌毒力的影响 鼻窦炎 项目总结/摘要 慢性鼻窦炎（CRS）是一种慢性气道疾病，定义为持续性炎症和鼻窦炎感染。 鼻和鼻窦粘膜。微生物通过种间相互作用影响人类健康， 一系列的结果--有些是有益的，有些是有害的。破坏鼻窦中稳定的微生物群 并且病原体过度生长可导致良性微生物群落变得促炎和侵入。 铜绿假单胞菌是一种机会性革兰氏阴性细菌， 难治性CRS;铜绿假单胞菌CRS患者与症状缓解差和临床症状恶化相关 结果，导致并发症，如眼眶蜂窝织炎和脑脓肿，即使在非 免疫力低下的人。因此，确定铜绿假单胞菌毒力的潜在机制 CRS进展对于开发新的治疗策略至关重要。我们的目标是测试 假设粘蛋白发酵微生物促进铜绿假单胞菌的微生物毒力，导致 慢性呼吸道综合征的进展。 (1)评价体内铜绿假单胞菌毒力增强和CRS进展是否依赖于粘蛋白 B发酵。脆弱的我们预期CRS家兔接种野生型铜绿假单胞菌和野生型B。 fragilis表现出最严重的CRS表型，具有显著的组织浸润和毒力相关性， 基因/蛋白质标记物。 (2)为了确定粘蛋白发酵微生物如何调节铜绿假单胞菌的组织侵袭， 体外抗生素耐药性。我们希望确定调节抗生素耐药性的关键因素， 侵入人体组织。 我们希望这一提议能回答有关铜绿假单胞菌在枸橼酸中毒力的基本问题， 破坏性CRS，这反过来可以导致开发新的，有效的治疗策略， 造成了巨大的医疗负担。拟议的实验也将揭示如何相互作用与 粘蛋白发酵微生物影响与铜绿假单胞菌相关的其他气道疾病，如恶性呼吸道疾病， 外耳炎、囊性纤维化和慢性阻塞性肺病。

Title: Impact of mucin fermenting microbes on the virulence of Pseudomonas aeruginosa in chronic rhinosinusitis Project Summary/Abstract Chronic rhinosinusitis (CRS) is a chronic airway disease defined as persistent inflammation and infection of the nasal and sinus mucosa. Microbes affect human health through interspecies interactions, with a broad spectrum of outcomes - some beneficial, others pathogenic. Disruption of the stable microbiota in the sinuses and pathogen overgrowth can lead to benign microbial communities becoming pro-inflammatory and invasive. Pseudomonas aeruginosa is an opportunistic, gram-negative bacterial species associated with severe, recalcitrant CRS; CRS patients with P. aeruginosa correlate with poor symptom resolution and worse clinical outcomes, leading to complications, such as orbital cellulitis and brain abscess, even in non- immunocompromised individuals. Thus, identifying the mechanisms underlying the virulence of P. aeruginosa in CRS progression is critical to developing new treatment strategies. Our aims are designed to test a hypothesis that mucin-fermenting microbes promote the microbial virulence of P. aeruginosa, leading to the progression of recalcitrant CRS. (1) To evaluate whether enhanced P. aeruginosa virulence and CRS progression in vivo rely on mucin fermentation by B. fragilis. We expect CRS rabbits inoculated with wild-type P. aeruginosa and wild-type B. fragilis to exhibit the most severe CRS phenotype with marked tissue invasion and virulence-associated gene/protein markers. (2) To determine how mucin-fermenting microbes modulate P. aeruginosa tissue invasion and antibiotic resistance in vitro. We expect to identify the critical actors in modulating antibiotic resistance and invasion in human tissue. We expect this proposal to answer fundamental questions regarding P. aeruginosa virulence in recalcitrant, destructive CRS, which, in turn, can lead to develop new, effective treatment strategies for a disease that exacts an enormous healthcare burden. The proposed experiments will also shed light on how interactions with mucin-fermenting microbes influence other airway diseases associated with P. aeruginosa, such as malignant otitis externa, cystic fibrosis, and chronic obstructive pulmonary disease.