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

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...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 105; no. 43; pp. 16761 - 16766
Main Authors Banin, Ehud, Lozinski, Alina, Brady, Keith M, Berenshtein, Eduard, Butterfield, Phillip W, Moshe, Maya, Chevion, Mordechai, Greenberg, Everett Peter, Banin, Eyal
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 28.10.2008
National Acad Sciences
Subjects
Animals
Anti-Bacterial Agents - pharmacology
Anti-Bacterial Agents - therapeutic use
Antibiotics
Bacteria
Biofilms
Biofilms - drug effects
Biological Sciences
Cornea
Deferoxamine - pharmacology
Deferoxamine - therapeutic use
Drug therapy
Drug Therapy, Combination
Eye Infections, Bacterial - drug therapy
Eyes
Gallium
Gentamicins - pharmacology
Gentamicins - therapeutic use
Infections
Iron
Iron - metabolism
Keratitis
Pathogens
Pseudomonas aeruginosa
Pseudomonas aeruginosa - drug effects
Pseudomonas Infections - drug therapy
Rabbits
Treatment Outcome
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Summary: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.
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Contributed by Everett Peter Greenberg, September 2, 2008
E.P.G. and Eyal Banin contributed equally to this work.
Author contributions: Ehud Banin, A.L., E. Berenshtein, P.W.B., M.M., M.C., E.P.G., and Eyal Banin designed research; Ehud Banin, A.L., K.M.B., E. Berenshtein, P.W.B., and M.M. performed research; Ehud Banin, E. Berenshtein, and M.C. contributed new reagents/analytic tools; Ehud Banin, A.L., K.M.B., E. Berenshtein, P.W.B., M.M., M.C., E.P.G., and Eyal Banin analyzed data; and Ehud Banin, A.L., M.C., E.P.G., and Eyal Banin wrote the paper.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0808608105