PSEUDOMONAS AERUGINOSA TYPE III SECRETION IN CYSTIC FIBROSIS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。进行性阻塞性肺疾病是超过90%的囊性纤维化患者的死亡原因。随着年龄的增长，肺功能的下降与呼吸道的铜绿假单胞菌感染有关。最近对革兰氏阴性细菌的研究发现了一种蛋白质输出系统，称为“III型分泌”，将毒素直接注入宿主细胞。这些效应蛋白的分泌与包括呼吸机相关性肺炎在内的急性PA感染的不良临床结局有关，但它们在CF肺部疾病中的作用尚未被探讨。研究III型分泌物在慢性阻塞性肺疾病中的作用有助于我们理解PA介导的肺损伤的发病机制。在这项研究中，我们将有两个具体的目标。具体目标1：在三年的时间里，研究儿童和成人CF呼吸道分离株中铜绿假单胞菌III型分泌物表型的流行率和稳定性。具体目标2：确定分泌型III型铜绿假单胞菌的存在是否预示着CF患者肺功能恶化得更快

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Progressive obstructive pulmonary disease is the cause of death in more than 90% of cystic fibrosis (CF) patients. Decline in pulmonary function with increasing age is associated with Pseudomonas aeruginosa (PA) infection of the airways. Recent studies of gram-negative bacteria have identified a protein export system, termed "type III secretion," that injects toxins directly into host cells. Secretion of these effector proteins has been associated with poor clinical outcomes in acute PA infections, including ventilator-associated pneumonia, but their role in CF lung disease has not been explored. Characterization of the role of type III secretion in CF lung disease may aid in our understanding of the pathogenesis of PA-mediated lung damage. In this study we will have two specific aims. Specific Aim 1: To characterize the prevalence and stability of the P. aeruginosa type III secretion phenotype in respiratory isolates from children and adults with CF over a three-year period. Specific Aim 2: To determine whether the presence of type-III-secreting P. aeruginosa isolates predicts a more rapid deterioration in lung function in CF patients