Effects of Reduced Mucus Oxygen Concentration in Airway Pseudomonas Infections of Cystic Fibrosis Patients

J Clin Invest. 2002 Feb;109(3):317-25. doi: 10.1172/JCI13870.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aerobiosis
  • Anaerobiosis
  • Cystic Fibrosis / complications*
  • Cystic Fibrosis / metabolism*
  • Cystic Fibrosis / microbiology
  • Female
  • Humans
  • Hypoxia / metabolism
  • Hypoxia / microbiology
  • Male
  • Microscopy, Electron, Scanning
  • Models, Biological
  • Mucus / metabolism*
  • Mucus / microbiology
  • Oxygen / metabolism*
  • Pseudomonas Infections / complications*
  • Pseudomonas Infections / metabolism*
  • Pseudomonas Infections / microbiology
  • Pseudomonas aeruginosa / growth & development
  • Pseudomonas aeruginosa / pathogenicity
  • Respiratory Tract Diseases / complications*
  • Respiratory Tract Diseases / metabolism*
  • Respiratory Tract Diseases / microbiology

Substances

  • Oxygen