title: Effects of reduced mucus oxygen concentration in airway Pseudomonas infections of cystic fibrosis patients.
abstract: Current theories of CF pathogenesis predict different predisposing "local environmental" conditions and sites of bacterial infection within CF airways. Here we show that, in CF patients with established lung disease, Pseudomonas aeruginosa was located within hypoxic mucopurulent masses in airway lumens. In vitro studies revealed that CF-specific increases in epithelial O(2) consumption, linked to increased airway surface liquid (ASL) volume absorption and mucus stasis, generated steep hypoxic gradients within thickened mucus on CF epithelial surfaces prior to infection. Motile P. aeruginosa deposited on CF airway surfaces penetrated into hypoxic mucus zones and responded to this environment with increased alginate production. With P. aeruginosa growth in oxygen restricted environments, local hypoxia was exacerbated and frank anaerobiosis, as detected in vivo, resulted. These studies indicate that novel therapies for CF include removal of hypoxic mucus plaques and antibiotics effective against P. aeruginosa adapted to anaerobic environments.
authors.affiliation: Institute of General and Environmental Hygiene, University of Tübingen, Tübingen, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Worlitzsch
authors.forename: Robert
authors.initials: R
authors.lastname: Tarran
authors.forename: Martina
authors.initials: M
authors.lastname: Ulrich
authors.forename: Ute
authors.initials: U
authors.lastname: Schwab
authors.forename: Aynur
authors.initials: A
authors.lastname: Cekici
authors.forename: Keith C
authors.initials: KC
authors.lastname: Meyer
authors.forename: Peter
authors.initials: P
authors.lastname: Birrer
authors.forename: Gabriel
authors.initials: G
authors.lastname: Bellon
authors.forename: Jürgen
authors.initials: J
authors.lastname: Berger
authors.forename: Tilo
authors.initials: T
authors.lastname: Weiss
authors.forename: Konrad
authors.initials: K
authors.lastname: Botzenhart
authors.forename: James R
authors.initials: JR
authors.lastname: Yankaskas
authors.forename: Scott
authors.initials: S
authors.lastname: Randell
authors.forename: Richard C
authors.initials: RC
authors.lastname: Boucher
authors.forename: Gerd
authors.initials: G
authors.lastname: Döring
mesh_terms: D000328:Adult; D000332:Aerobiosis; D000693:Anaerobiosis; D003550:Cystic Fibrosis / Q000150:complications* / Q000378:metabolism* / Q000382:microbiology; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000378:metabolism / Q000382:microbiology; D008297:Male; D008855:Microscopy, Electron, Scanning; D008954:Models, Biological; D009093:Mucus / Q000378:metabolism* / Q000382:microbiology; D010100:Oxygen / Q000378:metabolism*; D011552:Pseudomonas Infections / Q000150:complications* / Q000378:metabolism* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000254:growth & development / Q000472:pathogenicity; D012140:Respiratory Tract Diseases / Q000150:complications* / Q000378:metabolism* / Q000382:microbiology
chemical_list: D010100:Oxygen