Proceedings of the National Academy of Sciences · 2008 · 252 citations · 26 references
Veterinary MedicineInfectious DiseasesMicrobiologyAntimicrobial PharmacologyDrug DeliveryMedical MicrobiologyAntibiotic ResistanceAntimicrobial TherapyBiofilm Formation In InfectionCombination Antimicrobial TherapyOcular Antimicrobial TherapyTargeted Antimicrobial TherapyAnti-biofilm StrategiesBiofilm DisruptionBiofilm InhibitorsBiofilm-disrupting AgentsInhibitors Of Biofilm FormationTopical Antimicrobial AgentsTopical Antimicrobial PreparationsTopical Application
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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The Involvement of Cell-to-Cell Signals in the Development of a Bacterial Biofilm
David G. Davies, Matthew R. Parsek, James P. Pearson et al. · Science · 1998 · 3.4K citations