The ΔF508-CFTR mutation results in increased biofilm formation by Pseodomonas aeruginosa by increasing iron availability Moreau-Marquis, Sophie, Bomberger, Jennifer M., Anderson, Gregory G., Swiatecka-Urban, Agnieszka, Ye, Siying, O'Toole, George A. and Stanton, Bruce A. 2008, The ΔF508-CFTR mutation results in increased biofilm formation by Pseodomonas aeruginosa by increasing iron availability, American journal of physiology : lung cellular and molecular physiology, vol. 295, no. 1, pp. 25-37, doi: 10.1152/ajplung.00391.2007. Attached Files Name Description MIMEType Size Downloads Title The ΔF508-CFTR mutation results in increased biofilm formation by Pseodomonas aeruginosa by increasing iron availability Author(s) Moreau-Marquis, Sophie Bomberger, Jennifer M. Anderson, Gregory G. Swiatecka-Urban, Agnieszka Ye, Siying orcid.org/0000-0002-0882-1642 O'Toole, George A. Stanton, Bruce A. Journal name American journal of physiology : lung cellular and molecular physiology Volume number 295 Issue number 1 Start page 25 End page 37 Total pages 13 Publisher American Physiological Society Place of publication Bethesda, Md. Publication date 2008-07 ISSN 1040-0605 Keyword(s) cystic fibrosis transmembrane conductance regulator airway Summary 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 ΔF508-CFTR significantly enhanced P. aeruginosa biofilm formation, and ΔF508 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 ΔF508-CFTR cells was due to increased Fe release by airway cells. We found that airway cells expressing ΔF508-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 ΔF508-CFTR mutation enhances biofilm formation, in part, by increasing Fe release into the apical medium. Language eng DOI 10.1152/ajplung.00391.2007 Field of Research 119999 Medical and Health Sciences not elsewhere classified Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences HERDC Research category C1.1 Refereed article in a scholarly journal Copyright notice ©2008, American Physiological Society Persistent URL http://hdl.handle.net/10536/DRO/DU:30040953 Document type: Journal Article Collections: Faculty of Health School of Medicine Related Links Link Description Connect to published version (restricted access) Go to link with your DU access privileges     Unless expressly stated otherwise, the copyright for items in DRO is owned by the author, with all rights reserved. Versions Version Filter Type Wed, 07 Dec 2011, 10:05:25 EST Wed, 18 Jan 2012, 10:23:02 EST Wed, 18 Jan 2012, 10:25:54 EST Mon, 20 Feb 2012, 08:22:52 EST Wed, 20 Aug 2014, 10:09:16 EST Thu, 11 Dec 2014, 17:33:35 EST Filtered Full Citation counts:   Cited 131 times in TR Web of Science Cited 136 times in Scopus Search Google Scholar Access Statistics: 364 Abstract Views, 2 File Downloads  -  Detailed Statistics Created: Wed, 07 Dec 2011, 10:05:25 EST