This Article Full Text Full Text (PDF) All Versions of this Article: 2008-0299OCv1 41/3/305    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Google Scholar Articles by Moreau-Marquis, S. Articles by Stanton, B. A. PubMed PubMed Citation Articles by Moreau-Marquis, S. Articles by Stanton, B. A.

Tobramycin and FDA-Approved Iron Chelators Eliminate Pseudomonas aeruginosa Biofilms on Cystic Fibrosis Cells

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

Correspondence and requests for reprints should be addressed to Sophie Moreau-Marquis, Ph.D., Department of Physiology, Dartmouth Medical School, Hanover, NH 03755. E-mail: Sophie.Marquis{at}Dartmouth.edu

The ability of Pseudomonas aeruginosa to form antibiotic-resistant biofilms is thought to account for the inability of current therapies to resolve bacterial infections in the lungs of patients with cystic fibrosis (CF). We recently described a system in which highly antibiotic-resistant P. aeruginosa biofilms grow on human CF airway epithelial cells, and using this system we showed that enhanced iron release from CF cells facilitates the development of such highly antibiotic-resistant biofilms. Given the positive role for iron in biofilm development, we investigated whether the FDA-approved iron chelators deferoxamine and deferasirox would enhance the ability of tobramycin, the primary antibiotic used to treat CF lung infections, to eliminate P. aeruginosa biofilms. The combination of tobramycin with deferoxamine or deferasirox reduced established biofilm biomass by approximately 90% and reduced viable bacteria by 7-log units. Neither tobramycin nor deferoxamine nor deferasirox alone had such a marked effect. The combination of tobramycin and FDA-approved iron chelators also prevented the formation of biofilms on CF airway cells. These data suggest that the combined use of tobramycin and FDA-approved iron chelators may be an effective therapy to treat patients with CF and other lung disease characterized by antibiotic-resistant P. aeruginosa biofilms.

Key Words: antibiotic resistance • biofilms • deferoxamine • deferasirox • cystic fibrosis model

CLINICAL RELEVANCE This study shows that FDA-approved iron chelators can potentiate the tobramycin-mediated killing of Pseudomonas aeruginosa biofilms grown in a cystic fibrosis co-culture model. This is the first report of an effective therapeutic approach to kill antibiotic-resistant bacterial biofilms established on live cystic fibrosis airway epithelial cells.

 

This article has been cited by other articles:

				D. W. Reid, G. J. Anderson, and I. L. Lamont Role of lung iron in determining the bacterial and host struggle in cystic fibrosis Am J Physiol Lung Cell Mol Physiol, November 1, 2009; 297(5): L795 - L802. [Abstract] [Full Text] [PDF]