title: Nitric oxide-induced potentiation of the killing of Burkholderia cepacia by reactive oxygen species: implications for cystic fibrosis.
abstract: Burkholderia (formerly Pseudomonas) cepacia has emerged as an important pulmonary pathogen in cystic fibrosis, and survives within the lung despite a vigorous neutrophil-dominated immune response. Nitric oxide (NO) contributes to the antimicrobial activity of reactive oxygen species in the normal lung, but recent evidence suggests that inducible NO synthase is not expressed in the airway epithelial cells of cystic fibrosis (CF) patients. This may explain the failure of the neutrophil response to eliminate B. cepacia. To test this hypothesis, the present study examined the combined effect of NO, superoxide and H2O2 against B. cepacia. There was no killing of a highly transmissible strain by either superoxide or NO alone, but their combination reduced the bacterial count by >1000-fold over 75 min. This bactericidal activity was not sensitive to addition of superoxide dismutase, but was abrogated completely by catalase, suggesting that NO and hydrogen peroxide were the bactericidal mediators. Increased killing by NO in combination with H2O2 was seen for seven of a further 11 strains examined. The lack of NO in the lungs of CF patients may contribute to the survival of B. cepacia.
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Smith
authors.forename: John
authors.initials: J
authors.lastname: Green
authors.forename: Charlotte E
authors.initials: CE
authors.lastname: Eden
authors.forename: Malcolm L
authors.initials: ML
authors.lastname: Watson
mesh_terms: D016956:Burkholderia cepacia / Q000187:drug effects*; D003550:Cystic Fibrosis / Q000382:microbiology*; D004357:Drug Synergism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009569:Nitric Oxide / Q000494:pharmacology*; D017382:Reactive Oxygen Species
chemical_list: D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D006861:Hydrogen Peroxide