Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 105, Issue 43, Pages 16761-16766Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0808608105
Keywords
antimicrobials; biofilms; chronic infections; iron uptake; keratitis
Categories
Funding
- National Institutes of Allergy and Infectious Diseases [AI30040]
- US Cystic Fibrosis Foundation
- Bar-Ilan Nanotechnology Start-up Fund
- Israel Science Foundation [366/07, 316/05, 585/02]
- Yedidut Research
- Dr. Moshe and Paulina Bergman Memorial Fund
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The opportunistic pathogen Pseudomonas aeruginosa causes infections that are difficult to treat by antibiotic therapy. This bacterium can cause biofilm infections where it shows tolerance to antibiotics. Here we report the novel use of a metallo-complex, desferrioxaminegallium (DFO-Ga) that targets P. aeruginosa iron metabolism. This complex kills free-living bacteria and blocks biofilm formation. A combination of DFO-Ga and the anti-Pseudomonas antibiotic gentamicin caused massive killing of P. aeruginosa cells in mature biofilms. In a P. aeruginosa rabbit corneal infection, topical administration of DFO-Ga together with gentamicin decreased both infiltrate and final scar size by about 50% compared to topical application of gentamicin alone. The use of DFO-Ga as a Trojan horse delivery system that interferes with iron metabolism shows promise as a treatment for P. aeruginosa infections.
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