Reference strains of Mycobacteroides abscessus

脓肿分枝杆菌参考菌株

• 批准号: 10381458
• 负责人: Gyanu Lamichhane
• 金额: $ 23.97万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10381458
• 关键词: Abscess; Acid Fast Bacillae Staining Method; Acute; Aerosols; American Type Culture Collection; Animal Model; Antibiotic Resistance; Antibiotic susceptibility; Antibiotics; Archives; Bacteria; Bronchiectasis; Chronic; Chronic Obstructive Pulmonary Disease; Chronic lung disease; Clinical; Cystic Fibrosis; Data; Dermatology; Disease; Dose; Drug Evaluation; Genes; Genome; Genomic DNA; Growth; Human; In Vitro; Incidence; Individual; Infection; Intake; Journals; Knee; Lesion; Libraries; Lung; Lung diseases; Lung infections; Minimum Inhibitory Concentration measurement; Modeling; Mus; Mycobacterium abscessus; Nightmare; Organism; Pathology; Patient Representative; Patients; Pharmaceutical Preparations; Population; Predictive Value; Predisposition; Publishing; Regimen; Reporting; Research; Resistance; Sputum; Structure of parenchyma of lung; Subcutaneous abscess; Testing; Time; Toxic effect; United States National Institutes of Health; Virulent; acute infection; base; chronic infection; cystic fibrosis infection; cystic fibrosis patients; drug development; drug discovery; drug efficacy; emerging pathogen; insight; interest; mouse model; novel therapeutics; pre-clinical; programs; pulmonary function decline; reference genome; whole genome

PROJECT SUMMARY In cystic fibrosis, bronchiectasis and chronic obstructive pulmonary disease patients, non-tuberculous bacterium Mycobacteroides abscessus can cause chronic pulmonary disease that is often incurable and associated with rapid lung function decline. Additionally, existing treatment requires more than a year of daily intake of antibiotics with poor efficacies and significant toxicities. M. abscessus has been designated as an “antibiotic nightmare” and “an environmental bacterium turned clinical nightmare” due to extensive natural and acquired antibiotic resistance, which severely limits treatment options. Although the NIH recently declared M. abscessus as an emerging pathogen of interest, it is one of the least studied organisms. The overall aim of this proposal is to identify two clinical M. abscessus isolates that were recently derived from cystic fibrosis, bronchiectasis or chronic obstructive pulmonary disease patients and are representative of the strains relevant in the present context so that they can be used as reference strains in research. The historical M. abscessus strain that is currently used as the default reference strain was isolated in 1953 from a knee abscess. Therefore, it is unknown how relevant the data obtained using this will be to pulmonary infections and drug susceptibilities to strains prevalent today. Our central hypothesis is that reference strain(s) should represent current clinical isolates. We postulate a relevant reference strain is necessary for rigorous research so that the data obtained will be more applicable to M. abscessus infections in cystic fibrosis, bronchiectasis and chronic obstructive pulmonary disease patients.

项目摘要 在囊性纤维化、支气管扩张和慢性阻塞性肺疾病患者中， 结核分枝杆菌可引起慢性肺病，通常无法治愈， 与肺功能快速下降有关。此外，现有的治疗需要一年多的日常治疗， 抗生素摄入量大，疗效差，毒性大。M.阿维尼翁已被指定为 “抗生素噩梦”和“环境细菌变成临床噩梦”，由于广泛的自然 并获得抗生素耐药性，这严重限制了治疗选择。 尽管NIH最近宣布M.作为一种新兴的病原体感兴趣，它是一个最小的 研究有机体。本提案的总体目标是确定两个临床M。分离到的寄生虫 最近来自囊性纤维化、支气管扩张或慢性阻塞性肺病患者， 是本发明背景下相关菌株的代表，因此它们可用作参考菌株 在研究中。历史M。目前用作默认参考菌株的Escheressus菌株为 1953年从膝盖脓肿中分离出来因此，尚不清楚使用此方法获得的数据的相关性如何。 与肺部感染和药物敏感性有关。我们的核心假设是， 参考菌株应代表当前的临床分离株。我们假设相关参考菌株是 为了使所获得的数据更适用于M.尿道感染 囊性纤维化、支气管扩张和慢性阻塞性肺病患者。