The potential of desferrioxamine-gallium as an anti-Pseudomonas therapeutic agent

Ehud Banin, Alina Lozinski, Keith M. Brady, Eduard Berenshtein, Phillip W. Butterfield, Maya Moshe, Mordechai Chevion, Everett Peter Greenberg, Eyal Banin

Research output: Contribution to journalArticlepeer-review

213 Scopus citations

Abstract

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, desferrioxamine-gallium (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.

Original languageEnglish
Pages (from-to)16761-16766
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number43
DOIs
StatePublished - 28 Oct 2008

Keywords

  • Antimicrobials
  • Biofilms
  • Chronic infections
  • Iron uptake
  • Keratitis

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