Hypoxic mucus favors Pseudomonas infections in cystic fibrosis

Cystic fibrosis (CF) is life-threatening primarily because the lungs of affected individuals are subject to persistent and intractable infections, typically with Pseudomonas aeruginosa. The properties of the tracheal fluids that support these infections in CF patients has been a matter of debate, which has generated considerable interest in the ionic strength and volume of airway surface liquid (ASL) in healthy and CF lungs. Surprisingly, less attention has been paid to the properties of P. aeruginosa itself as it exists within the airway epithelium. Worlitzsch and coworkers show here that these bacteria do not adhere directly to the epithelial layer but can be found within the ASL in intact lungs, as well as within the mucus layer secreted by cultured respiratory epithelia. The authors also show that the thickened ASL in the lungs of CF patients is markedly anoxic, relative to that of healthy individuals or of patients with primary ciliary dyskinesia, another condition that leads to frequent bacterial infections. Although P. aeruginosa is an aerobic bacterium, this low oxygen level is not sufficient to prevent its growth, apparently because the ASL contains nitrates or other electron acceptors that can substitute for molecular oxygen. However, hypoxia induces a stress response in the bacteria, promoting a mucoid phenotype. As has been seen in other bacterial species, this transition may allow the bacteria to evade host defenses and even survive exposure to antibiotics. Worlitzsch et al. suggest that the growth of hypoxia-tolerant bacteria further depletes the oxygen, thus maintaining the ASL in the hypoxic state that appears to be characteristic of the CF lung.


Contact: John Ashkenas
Journal of Clinical Investigation

Page: 1

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