Bacterial cyanogenesis occurs in the cystic fibrosis lung

Abstract

The cystic fibrosis (CF) lung environment is poorly defined, but data suggest that bacteria may encounter reduced oxygen tensions and possibly an anaerobic environment. Pseudomonas aeruginosa produces the potent toxin cyanide under strictly microaerobic conditions. Evidence of bacterial cyanogenesis in the CF lung was investigated in the present study by measuring sputum cyanide concentrations.Sputum cyanide was measured in seven stable CF patients, as well as before and after intravenous antibiotic therapy during a hospital admission in a further eight patients experiencing acute exacerbations. All patients were chronically infected with P. aeruginosa. Comparative sputum data were obtained from nine CF patients with no documented P. aeruginosa infection and 10 healthy, nonsmoking normal controls.High levels of cyanide were detected in all the P. aeruginosa-infected stable CF patients (median (range) 0.56 (0.37-2.81) mg?mL -1 ), and in seven out of eight acute sputum samples (0.73 (0-1.43) mg?mL -1 ). In contrast, cyanide was not detectable in sputum from eight out of nine CF patients without P. aeruginosa infection or in any of the normal controls. Intravenous antibiotic treatment significantly reduced sputum cyanide levels (median 0.73 to median 0.0 mg?mL -1 ).The cyanide detected indicates that the cystic fibrosis lung provides a predominantly microaerobic environment for Pseudomonas aeruginosa. Cyanide is likely to be a potentially important virulence factor in Pseudomonas aeruginosa-infected cystic fibrosis patients.

Anaerobiosis-Induced Loss of Cytotoxicity Is Due to Inactivation of Quorum Sensing in Pseudomonas aeruginosa

“…This abnormally altered CF airway has been reported to harbor regions with a steep oxygen gradient ranging from aerobic to anaerobic (40,54). Given the fact that P. aeruginosa is able to grow anaerobically in the presence of alternative electron acceptors such as nitrate (NO 3 Ϫ ) or nitrite (NO 2 Ϫ ) that are present in sufficient quantity in a CF mucus layer (21,31,59), further research on bacterial responses to an anaerobic environment should be pursued for an integrated understanding of its virulence mechanisms.…”

Pseudomonas aeruginosa and cyanide production

“…This and the absence of cyanide from a small number of sputum/breath samples from P. aeruginosa infected patients [5][6][7] suggest that cyanide production is dependent on the presence of specific P. aeruginosa strains as well as the total P. aeruginosa load. This theory that cyanide production varies between P. aeruginosa genotypes is supported by the finding that the Liverpool epidemic P. aeruginosa strain overproduces certain quorum sensing regulated exoproducts such as LasA protease and elastase [19].…”

“…Cyanide has also been identified in the sputum [5,6] and HCN in the breath of CF and non-CF bronchiectasis patients infected with P. aeruginosa [5,7]. Conversely, cyanide is absent from the sputum of bronchiectasis patients without P. aeruginosa infection [5,6] and HCN is very low or absent from the breath of healthy children [8]. Studies in healthy adults have shown that much of the HCN is generated in the mouth and this could have importance when measuring HCN in exhaled breath in relation to infection with P. aeruginosa [9].…”

“…If this was correct, however, any organism in the lower respiratory tract causing widespread airway inflammation would lead to cyanide production and yet, cyanide has been shown to be absent from the sputum of CF and non-CF bronchiectasis patients infected with organisms other than P. aeruginosa [5,6].…”

“…The high P. aeruginosa population density of CF mucus maximises quorum-sensing cyanide production and together with its low O 2 concentration and ideal temperature, provides the perfect environmental parameters for P. aeruginosa cyanogenesis. The high concentrations of cyanide identified in the sputum and breath of CF patients [5][6][7] may well affect lung cellular function within human lungs, contributing to the long-term damage known to result from chronic P. aeruginosa infection. It may also assist P. aeruginosa in excluding other lung pathogens leading to it being the dominant bacterium.…”