Nitric oxide-induced potentiation of the killing of Burkholderia cepacia by reactive oxygen species: implications for cystic fibrosis

Burkholderia (formerly Pseudomonas) cepacia has emerged as an important pul monary pathogen in cystic fibrosis, and survives within the lung despite a vigorous neutrophil-dominated immune response. Nitric oxide (NO) contribute s to the antimicrobial activity of reactive oxygen species in the normal lu ng, but recent evidence suggests that inducible NO synthase is not expresse d 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 combinatio n reduced the bacterial count by >1000-fold over 75 min. This bactericidal activity was not sensitive to addition of superoxide dismutase, but was abr ogated completely by catalase, suggesting that NO and hydrogen peroxide wer e the bactericidal mediators. Increased killing by NO in combination with H 2O2 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.