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

被引:205
作者
Banin, Ehud [1 ,2 ]
Lozinski, Alina [3 ]
Brady, Keith M. [4 ]
Berenshtein, Eduard [5 ]
Butterfield, Phillip W. [6 ]
Moshe, Maya [2 ]
Chevion, Mordechai [5 ]
Greenberg, Everett Peter [1 ]
Banin, Eyal [3 ]
机构
[1] Univ Washington, Sch Med, Dept Microbiol, Seattle, WA 98195 USA
[2] Bar Ilan Univ, Inst Nanotechnol & Adv Mat, Mina & Everard Goodman Fac Life Sci, IL-52900 Ramat Gan, Israel
[3] Hadassah Hebrew Univ Med Ctr, Dept Ophthalmol, IL-91120 Jerusalem, Israel
[4] Univ Iowa, Dept Microbiol, Roy & Lucille Carver Coll Med, Iowa City, IA 52242 USA
[5] Hebrew Univ Jerusalem, Dept Cellular Biochem & Human Genet, IL-91120 Jerusalem, Israel
[6] Washington State Univ, Dept Civil & Environm Engn, Spokane, WA 99210 USA
基金
以色列科学基金会;
关键词
antimicrobials; biofilms; chronic infections; iron uptake; keratitis;
D O I
10.1073/pnas.0808608105
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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, desferrioxaminegallium (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.
引用
收藏
页码:16761 / 16766
页数:6
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