期刊
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
卷 295, 期 1, 页码 L25-L37出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajplung.00391.2007
关键词
cystic fibrosis transmembrane conductance regulator; airway
资金
- NHLBI NIH HHS [HL-074175] Funding Source: Medline
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 Delta F508-CFTR significantly enhanced P. aeruginosa biofilm formation, and Delta 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 Delta F508-CFTR cells was due to increased Fe release by airway cells. We found that airway cells expressing Delta 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 Delta F508-CFTR mutation enhances biofilm formation, in part, by increasing Fe release into the apical medium.
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