Cystic fibrosis: ironing out the problem of infection?

THE STUDY BY MOREAU-MARQUIS et al. (3) in this issue of AJPLung advances our understanding of lung disease in cystic fibrosis (CF). Their findings are important because they may largely explain the peculiar propensity to early Pseudomonas aeruginosa infection that characterizes this most common of lethal genetic diseases. Moreau-Marquis et al. (3) demonstrate that immortalized human CF airway epithelial cells cocultured with P. aeruginosa promote the formation of antibiotic-resistant biofilms. Their series of experiments demonstrate that this is due to abnormal accumulation and loss of iron by CF epithelial cells and that biofilm formation can be prevented by either iron chelation therapy or by increasing normal cell membrane cystic fibrosis transmembrane regulator (CFTR) expression using the novel compound Corr4a. The observations of Moreau-Marquis et al. (3) confirm what has been clinically suspected in CF with respect to iron promotion of infection with P. aeruginosa. Previous studies have demonstrated that the airways of CF patients contain increased amounts of total iron and the iron-binding protein ferritin as well as a relationship between airway iron content and quantitative P. aeruginosa load assessed by colony-forming units per milliliter of sputum (5). This study also found an increase in iron in sputum in CF patients who had not previously been infected with P. aeruginosa, suggesting that elevated airway iron content may predate P. aeruginosa acquisition. Further evidence to support a problem with iron trafficking comes from the CF G551D mouse model. The teeth of these mice exhibit abnormal iron transport in pigment ameloblasts compared with wild-type mice, resulting in unusually white dentition (7). The study by Moreau-Marquis et al. (3) lends biological rationale to these earlier observations and brings two key questions into focus. First, what is the underlying link between abnormal or absent CFTR and cell iron homeostasis? Second, how does this impact on the CF host and P. aeruginosa interaction?