title: Pseudomonas aeruginosa pyocyanin inactivates lung epithelial vacuolar ATPase-dependent cystic fibrosis transmembrane conductance regulator expression and localization.
abstract: Pseudomonas aeruginosa (PA) is a major pathogen causing morbidity and ultimately mortality in patients afflicted with cystic fibrosis (CF) lung disease. One important virulence factor, pyocyanin (PCN), is a blue, redox-active compound that is secreted in such copious amounts by PA in the CF lungs that it determines the colour of expectorated sputum. In this study, we discovered that physiological concentrations of PCN inactivate the airway epithelial vacuolar ATPase, resulting in reduced expression and trafficking of the cystic fibrosis transmembrane conductance regulator in cultured lung and primary nasal epithelial cells. Our study supports the notion that PCN contributes significantly to the pathogenesis of CF and other bronchiectasis patients infected by PA.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Cincinnati Children's Hospital, Cincinnati, OH, USA.
authors.forename: Fansheng
authors.initials: F
authors.lastname: Kong
authors.forename: Lisa
authors.initials: L
authors.lastname: Young
authors.forename: Yi
authors.initials: Y
authors.lastname: Chen
authors.forename: Huimin
authors.initials: H
authors.lastname: Ran
authors.forename: Melanie
authors.initials: M
authors.lastname: Meyers
authors.forename: Patricia
authors.initials: P
authors.lastname: Joseph
authors.forename: You-Hee
authors.initials: YH
authors.lastname: Cho
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Hassett
authors.forename: Gee W
authors.initials: GW
authors.lastname: Lau
mesh_terms: D020746:Calcium Channels, L-Type / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D002478:Cells, Cultured; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology*; D053503:Epithelial Sodium Channels; D005786:Gene Expression Regulation / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D021381:Protein Transport / Q000187:drug effects; D011550:Pseudomonas aeruginosa / Q000378:metabolism / Q000472:pathogenicity*; D011710:Pyocyanine / Q000378:metabolism / Q000494:pharmacology*; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology*; D015222:Sodium Channels / Q000378:metabolism; D025262:Vacuolar Proton-Translocating ATPases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D020746:Calcium Channels, L-Type; D053503:Epithelial Sodium Channels; D015222:Sodium Channels; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D011710:Pyocyanine; D025262:Vacuolar Proton-Translocating ATPases