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EDITORIAL FOCUS

The F508-CFTR mutation results in increased biofilm formation by Pseudomonas aeruginosa by increasing iron availability

Departments of ¹Physiology and ²Microbiology and Immunology, Dartmouth Medical School, Hanover, New Hampshire

Submitted 19 September 2007 ; accepted in final form 20 March 2008

Enhanced antibiotic resistance of Pseudomonas aeruginosa in the cystic fibrosis (CF) lung is thought to be due to the formation of biofilms. However, there is no information on the antibiotic resistance of P. aeruginosa biofilms grown on human airway epithelial cells or on the effects of airway cells on biofilm formation by P. aeruginosa. Thus we developed a coculture model and report that airway cells increase the resistance of P. aeruginosa to tobramycin (Tb) by >25-fold compared with P. aeruginosa grown on abiotic surfaces. Therefore, the concentration of Tb required to kill P. aeruginosa biofilms on airway cells is 10-fold higher than the concentration achievable in the lungs of CF patients. In addition, CF airway cells expressing F508-CFTR significantly enhanced P. aeruginosa biofilm formation, and F508 rescue with wild-type CFTR reduced biofilm formation. Iron (Fe) content of the airway in CF is elevated, and Fe is known to enhance P. aeruginosa growth. Thus we investigated whether enhanced biofilm formation on F508-CFTR cells was due to increased Fe release by airway cells. We found that airway cells expressing F508-CFTR released more Fe than cells rescued with WT-CFTR. Moreover, Fe chelation reduced biofilm formation on airway cells, whereas Fe supplementation enhanced biofilm formation on airway cells expressing WT-CFTR. These data demonstrate that human airway epithelial cells promote the formation of P. aeruginosa biofilms with a dramatically increased antibiotic resistance. The F508-CFTR mutation enhances biofilm formation, in part, by increasing Fe release into the apical medium.

cystic fibrosis transmembrane conductance regulator; airway

This article has been cited by other articles:

				D. W. Reid, G. J. Anderson, and I. L. Lamont Cystic fibrosis: ironing out the problem of infection? Am J Physiol Lung Cell Mol Physiol, July 1, 2008; 295(1): L23 - L24. [Full Text] [PDF]