Studies on bacterial populations and therapeutics for CF lung infections

CF 肺部感染的细菌种群和治疗方法研究

• 批准号: 9101824
• 负责人: PRADEEP k SINGH
• 金额: $ 15.02万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2020-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9101824
• 关键词: Address; Adult; Antibiotic susceptibility; Antibiotics; Bacteria; Bacterial Infections; Cells; Child; Childhood; Chronic; Clinical Trials; Collaborations; Committee Members; Communicable Diseases; Core Facility; Critical Care; Cystic Fibrosis; DNA; Dermatology; Discipline; Disease; Environment; Epidemiology; Faculty; Failure; Fellowship; Fellowship Program; Funding; Genome; Goals; Gold; Grant; Heart; Hour; Infection; Infectious Diseases Research; Laboratories; Lung; Lung diseases; Measurement; Medical; Medicine; Mentors; Methods; Microbiology; Molecular; Molecular and Cellular Biology; Organism; Oropharyngeal; Outcomes Research; Pathogenesis; Patients; Pharyngeal structure; Phenotype; Population; Proteomics; Pseudomonas aeruginosa; Pulmonology; Research; Research Infrastructure; Research Personnel; Research Project Grants; Research Support; Resistance; Resources; Sampling; Science; Sputum; Taxon; Testing; Therapeutic; Time; Training; Translational Research; Transplantation; Universities; Wages; Washington; base; clinical practice; cystic fibrosis patients; improved; in vivo; interest; member; microbial; microbiome; microbiota; novel; novel strategies; pathogen; patient oriented research; predicting response; programs; public health relevance; research and development; skills; therapy resistant

 DESCRIPTION (provided by applicant): The goal of this K24 is to provide salary support for Dr. Singh to allow him to spend 40% of his time mentoring pulmonary and critical care fellows, junior faculty and other trainees in patient-oriented research on chronic airway infections. This proposal will enable Dr. Singh to expand his translational research program, integrate fellows and junior faculty in to the program, and provide protected time so that the can mentor additional MD fellows. The proposal also provides time and infrastructure to help Dr. Singh enhance his own mentoring skills. The two research projects described involve face-to-face interactions with patients Project 1 exploits preliminary findings which show that infecting P. aeruginosa strains evolve to produce genetically diverse but clonally-related populations within CF lungs, and that the relative abundance of subpopulations change as patients are treated with antibiotics. This is important because subpopulations that increase during treatment have phenotypes that enable them to resist treatment in vivo, while those that decrease lack resistance functions. Studying these subpopulations enable us to test novel hypotheses about the mechanisms enabling bacteria to withstand antibiotics in chronic infections. Project 2 exploits preliminary findings that show that upper airway contamination may confound DNA-based measurements of lung microbiota. Accurately identifying the bacteria causing CF infections is among the most important tasks in CF infection research. We propose using the novel "2-scope method", along with advanced analytic methods, to test the hypotheses that some of the taxa identified in upper airway samples from CF children using DNA-based methods are oropharyngeal contaminants, or are derived from non viable cells.

 描述（由申请人提供）：该 K24 的目标是为 Singh 博士提供薪资支持，使他能够花 40% 的时间指导肺部和重症监护研究员、初级教员和其他受训人员进行以患者为导向的慢性气道感染研究。该提案将使辛格博士能够扩大他的转化研究计划，将研究员和初级教师纳入该计划，并提供受保护的时间，以便他们能够指导更多的医学博士研究员。该提案还提供时间和基础设施来帮助辛格博士提高自己的指导技能。所描述的两个研究项目涉及与患者面对面的互动。项目 1 利用的初步发现表明，感染铜绿假单胞菌菌株进化为在 CF 肺内产生遗传多样性但克隆相关的群体，并且亚群体的相对丰度随着患者接受抗生素治疗而变化。这很重要，因为治疗期间增加的亚群具有使它们能够抵抗体内治疗的表型，而减少的亚群则缺乏抵抗功能。研究这些亚群使我们能够测试关于细菌在慢性感染中抵抗抗生素的机制的新假设。项目 2 利用的初步结果表明，上呼吸道污染可能会混淆基于 DNA 的肺部微生物群测量结果。准确识别引起CF感染的细菌是CF感染研究中最重要的任务之一。我们建议使用新颖的“2-scope 方法”以及先进的分析方法来检验以下假设：使用基于 DNA 的方法在 CF 儿童上呼吸道样本中鉴定出的一些类群是口咽污染物，或者源自非存活细胞。