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 in | Proceedings of the National Academy of Sciences - PNAS Vol. 105; no. 43; pp. 16761 - 16766 |
|---|---|
| Main Authors | , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
National Academy of Sciences
28.10.2008
National Acad Sciences |
| Subjects | |
| Online Access | Get full text |
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| 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. |
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| AbstractList | The opportunistic pathogen Pseudoinonas 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 ofF. 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 Troj an horse delivery system that interferes with iron metabolism shows promise as a treatment for P. aeruginosa infections. [PUBLICATION 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. 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. 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. antimicrobials biofilms chronic infections iron uptake keratitis |
| Author | Lozinski, Alina Brady, Keith M Greenberg, Everett Peter Chevion, Mordechai Banin, Eyal Moshe, Maya Berenshtein, Eduard Banin, Ehud Butterfield, Phillip W |
| Author_xml | – sequence: 1 fullname: Banin, Ehud – sequence: 2 fullname: Lozinski, Alina – sequence: 3 fullname: Brady, Keith M – sequence: 4 fullname: Berenshtein, Eduard – sequence: 5 fullname: Butterfield, Phillip W – sequence: 6 fullname: Moshe, Maya – sequence: 7 fullname: Chevion, Mordechai – sequence: 8 fullname: Greenberg, Everett Peter – sequence: 9 fullname: Banin, Eyal |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/18931304$$D View this record in MEDLINE/PubMed |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 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. |
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| Snippet | The opportunistic pathogen Pseudomonas aeruginosa causes infections that are difficult to treat by antibiotic therapy. This bacterium can cause biofilm... The opportunistic pathogen Pseudomonas aeruginosa causes infections that are difficult to treat by antibiotic therapy. This bacterium can cause biofilm... The opportunistic pathogen Pseudoinonas aeruginosa causes infections that are difficult to treat by antibiotic therapy. This bacterium can cause biofilm... |
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| SubjectTerms | 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 |
| Title | potential of desferrioxamine-gallium as an anti-Pseudomonas therapeutic agent |
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