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

粘蛋白发酵微生物对慢性鼻窦炎铜绿假单胞菌毒力的影响

• 批准号: 10611454
• 负责人: Do-Yeon Cho
• 金额: $ 18.56万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-19 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10611454
• 关键词: Acceleration; Adult; Affect; Airway Disease; American; Antibiotic Resistance; Antibiotics; Asthma; Bacterial Genes; Bacteroides fragilis; Benign; Brain Abscess; CT2584 HMS; Carbon; Cellulitis; Chronic Bronchitis; Chronic Disease; Chronic Obstructive Pulmonary Disease; Clinical; Congestive Heart Failure; Cystic Fibrosis; DNA Probes; Data; Digoxin; Disease; Environment; Enzymes; Epithelium; Epoxide hydrolase; Exhibits; Eye Infections; Fermentation; Gene Expression; Genes; Gram-Negative Bacteria; Growth; Health; Healthcare; Human; Impairment; In Situ Hybridization; In Vitro; Individual; Infection; Inflammation; Inflammatory; Invaded; Irrigation; Isocitrate Lyase; Label; Liquid substance; Macrophage; Malignant - descriptor; Measurement; Methods; Microbe; Modeling; Mucins; Mucous Membrane; National Institute of Allergy and Infectious Disease; Nose; Nutrient; Operative Surgical Procedures; Oryctolagus cuniculus; Otitis Externa; Outcome; Pathogenicity; Patients; Peptic Ulcer; Phenotype; Population; Proliferating; Pseudomonas aeruginosa; Pseudomonas aeruginosa infection; Pyruvate synthase; Quality of life; Research; Research Personnel; Resolution; Ribosomal RNA; Role; Saline; Sinus; Source; Steroid therapy; Streptococcus; Submucosa; Symptoms; System; Techniques; Testing; Tissues; Translating; Virulence; Virulence Factors; bone erosion; care burden; chronic respiratory disease; chronic rhinosinusitis; design; effective therapy; experimental study; human tissue; in vivo; microbial; microbial community; microbiota; mutant; novel; novel therapeutic intervention; pathogen; protein biomarkers; protein expression; response; transcriptome sequencing; treatment strategy

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.

题目：黏素发酵菌对慢性铜绿假单胞菌毒力的影响

项目成果

A preclinical model to tackle chronic rhinosinusitis.

解决慢性鼻窦炎的临床前模型。

• DOI: 10.1002/alr.22768
• 发表时间: 2021
• 期刊: International forum of allergy & rhinology
• 影响因子: 6.4
• 作者: Cho,Do-Yeon;Douglas,RichardG
• 通讯作者: Douglas,RichardG

Inappropriate image duplications in rhinology research publications.

鼻学研究出版物中存在不恰当的图像重复。

• DOI: 10.1002/alr.23226
• 发表时间: 2024
• 期刊: International forum of allergy & rhinology
• 影响因子: 6.4
• 作者: Cho,Do-Yeon;Bishop,Jessica;Grayson,Jessica;Woodworth,BradfordA
• 通讯作者: Woodworth,BradfordA

The Olfactory System: Basic Anatomy and Physiology for General Otorhinolaryngologists.

• DOI: 10.21053/ceo.2023.00185
• 发表时间: 2023-11
• 期刊: Clinical and experimental otorhinolaryngology
• 影响因子: 3

Gabapentin improves parosmia after COVID-19 infection.

加巴喷丁可改善 COVID-19 感染后的嗅觉异常。

• DOI: 10.1002/alr.23117
• 发表时间: 2023
• 期刊: International forum of allergy & rhinology
• 影响因子: 6.4
• 作者: Garcia,JaimeAPena;Miller,Emily;Norwood,TimothyG;Dorin,NatalieA;Grayson,Jessica;Woodworth,Bradford;Cho,Do-Yeon
• 通讯作者: Cho,Do-Yeon