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Proc Natl Acad Sci U S A. 2008 Oct 28;105(43):16761-6. doi: 10.1073/pnas.0808608105. Epub 2008 Oct 17.

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

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1
Department of Microbiology, School of Medicine, University of Washington, Seattle, WA 98195, USA.

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.

PMID:
18931304
PMCID:
PMC2575493
DOI:
10.1073/pnas.0808608105
[Indexed for MEDLINE]
Free PMC Article
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