PSEUDOMONAS AERUGINOSA TYPE III SECRETION IN CYSTIC FIBROSIS

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。进行性阻塞性肺疾病是超过90%的囊性纤维化（CF）患者的死亡原因。随着年龄的增长，肺功能下降与呼吸道铜绿假单胞菌（PA）感染有关。最近对革兰氏阴性细菌的研究已经确定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急性PA感染（包括呼吸机相关性肺炎）的不良临床结局相关，但其在CF肺病中的作用尚未探讨。III型分泌物在CF肺疾病中的作用的特征可能有助于我们理解PA介导的肺损伤的发病机制。在这项研究中，我们将有两个具体目标。具体目标1：描述3年内CF儿童和成人呼吸道分离株中铜绿假单胞菌III型分泌表型的流行率和稳定性。具体目标二：确定分泌III型铜绿假单胞菌分离株的存在是否预示CF患者的肺功能更快恶化

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