Studies on bacterial populations and therapeutics for CF lung infections

 描述（由申请人提供）：该K24的目标是为Singh博士提供工资支持，使他能够将40%的时间用于指导肺部和重症监护研究员，初级教师和其他学员进行以患者为导向的慢性气道感染研究。这一提议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，以便指导更多的医学博士研究员。该提案还提供了时间和基础设施，以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的面对面互动。项目1利用了初步发现，这些发现表明感染铜绿假单胞菌菌株在CF肺内进化产生遗传多样性但克隆相关的种群，并且随着患者接受抗生素治疗，亚群的相对丰度发生变化。这一点很重要，因为在治疗期间增加的亚群具有使其能够抵抗体内治疗的表型，而那些减少的亚群缺乏抵抗功能。研究这些亚群使我们能够测试关于细菌在慢性感染中耐受抗生素的机制的新假设。项目2利用了初步发现，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。准确鉴定引起CF感染的细菌是CF感染研究中最重要的任务之一。我们建议使用新的“2-scope方法”，沿着与先进的分析方法，以测试的假设，即一些分类鉴定的上气道样本CF儿童使用DNA为基础的方法是口咽污染物，或来自非活细胞。

 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.