In the healthy lung the opportunistic pathogen, Pseudomonas aeruginosa, is rapidly eliminated by mucociliary clearance, a process that is dependent on the activity of the CFTR anion channel that, in concert with a number of other transport proteins, regulates the volume and composition of the periciliary surface liquid. This fluid layer is essential to enable cilia to clear pathogens from the lungs. However, in cystic fibrosis (CF), mutations in the CFTR gene reduce Cl and HCO3 secretion, thereby decreasing periciliary surface liquid volume and mucociliary clearance of bacteria. In CF this leads to persistent infection by P. aeruginosa, which is the cause of reduced lung function and death in ~95% of CF patients. Studies in our laboratory have shown that P. aeruginosa inhibits both wt CFTR Cl secretion and drug rescued Phe508del CFTR Cl secretion and the inflammatory response to infection by secreting outer membrane vesicles that contain virulence factors and siRNA. By contrast, airway epithelial cells secrete extracellular vesicles (EV) containing miRNA that increase the sensitivity of P. aeruginosa to antibiotics, thereby reducing the infection. This bi-directionsl communication between the host and pathogen is mediated by extracellular vesicles.
This event is part of the Department of Physiology Friday Seminar Series and is sponsored by the Cystic Fibrosis Translational Research Centre.
This seminar will be given online via Zoom. Details in attached poster.