Effects of reduced mucus oxygen concentration in airway Pseudomonas infections of cystic fibrosis patients.
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.
Worlitzsch
Dieter
D
Institute of General and Environmental Hygiene, University of Tübingen, Tübingen, Germany.
Tarran
Robert
R
Ulrich
Martina
M
Schwab
Ute
U
Cekici
Aynur
A
Meyer
Keith C
KC
Birrer
Peter
P
Bellon
Gabriel
G
Berger
Jürgen
J
Weiss
Tilo
T
Botzenhart
Konrad
K
Yankaskas
James R
JR
Randell
Scott
S
Boucher
Richard C
RC
Döring
Gerd
G
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
D010100:Oxygen