Molecular basis for defective glycosylation and Pseudomonas pathogenesis in cystic fibrosis lung.
نویسندگان
چکیده
The CFTR gene encodes a transmembrane conductance regulator, which is dysfunctional in patients with cystic fibrosis (CF). The mechanism by which defective CFTR (CF transmembrane conductance regulator) leads to undersialylation of plasma membrane glycoconjugates, which in turn promote lung pathology and colonization with Pseudomonas aeruginosa causing lethal bacterial infections in CF, is not known. Here we show by ratiometric imaging with lumenally exposed pH-sensitive green fluorescent protein that dysfunctional CFTR leads to hyperacidification of the trans-Golgi network (TGN) in CF lung epithelial cells. The hyperacidification of TGN, glycosylation defect of plasma membrane glycoconjugates, and increased P. aeruginosa adherence were corrected by incubating CF respiratory epithelial cells with weak bases. Studies with pharmacological agents indicated a role for sodium conductance, modulated by CFTR regulatory function, in determining the pH of TGN. These studies demonstrate the molecular basis for defective glycosylation of lung epithelial cells and bacterial pathogenesis in CF, and suggest a cure by normalizing the pH of intracellular compartments.
منابع مشابه
A Review of The Role of The Microbiome on Immune Responses and Its Association With Cystic Fibrosis
In recent years, the microbiome has been recognized as a key regulator of immune responses. Evidence suggests that changes in the microbiome can lead to chronic disease and even exacerbation of the disease. Impairment of innate immunity resulting from microbial incompatibility may worsen host susceptibility to infection and exacerbate chronic lung diseases. Specific microbes play a key role in ...
متن کاملGenetic Profiling of Pseudomonas aeruginosa Isolates from Iranian Patients with Cystic Fibrosis Using RAPD-PCR and PFGE
Objective(s) Pseudomonas aeruginosa is the most important cause of chronic lung infections and death in patients with cystic fibrosis. Determining the distribution of specific strains within patient populations is important in order to examine the epidemiology of the disease and the possibility of cross infection among patients. Materials and Methods Forty six Iranian patients with cystic fib...
متن کاملEvaluation of Antibiotic Resistance Trend among Cystic Fibrosis Patients: A Single Center Study from 2014-2019
Background: Antibiotic resistance in Cystic Fibrosis (CF) patients has been a serious issue in their survival. The objective of this study was to investigate the antibiogram trend in serial admissions among CF patients. Materials and Methods: In this retrospective descriptive-analytical study, from 2014 to 2019, 95 known cases of CF pati...
متن کاملAntibiotic resistance properties and molecular characterization of Pseudomonas aeruginosa strains from patients with cystic fibrosis (CF) referred to Gholhak Pathobiology Laboratory in Tehran city during 2016-2018
Background and Objectives: Pseudomonas aeruginosa isolates from the lungs of cystic fibrosis (CF) patients are often heterogeneous and antibiotic resistant strains. Our work therefore focused on the antibiotic resistance properties of these P. aeruginosa strains isolated from Iranian patients, as well as the genetic diversity analysis by a repetitive-element-based molecular assay. Methods: This ...
متن کاملType IV pilus glycosylation mediates resistance of Pseudomonas aeruginosa to opsonic activities of the pulmonary surfactant protein A.
Pseudomonas aeruginosa is a major bacterial pathogen commonly associated with chronic lung infections in cystic fibrosis (CF). Previously, we have demonstrated that the type IV pilus (Tfp) of P. aeruginosa mediates resistance to antibacterial effects of pulmonary surfactant protein A (SP-A). Interestingly, P. aeruginosa strains with group I pilins are O-glycosylated through the TfpO glycosyltra...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Proceedings of the National Academy of Sciences of the United States of America
دوره 98 24 شماره
صفحات -
تاریخ انتشار 2001