Desferrioxamine and desferrioxamine-caffeine as carriers of aluminum and gallium to microbes via the Trojan Horse Effect

被引:21
作者
Alvarado Huayhuaz, Jesus Antonio [1 ]
Vitorino, Hector Aguilar [1 ]
Campos, Othon Souto [1 ]
Pires Serrano, Silvia Helena [1 ]
Kaneko, Telma Mary [2 ]
Esposito, Breno Pannia [1 ]
机构
[1] Univ Sao Paulo, Inst Chem, Dept Fundamental Chem, Av Prof Lineu Prestes 748, BR-05508000 Sao Paulo, SP, Brazil
[2] Univ Sao Paulo, Fac Pharmaceut Sci, Sao Paulo, SP, Brazil
基金
巴西圣保罗研究基金会;
关键词
Desferrioxamine; Aluminum; Gallium; Caffeine; Trojan horse; IRON CHELATORS; SIDEROPHORES; TRANSPORT; EQUILIBRIUM; DELIVERY; OVERLOAD; COMPLEX; CELLS;
D O I
10.1016/j.jtemb.2017.01.006
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Iron acquisition by bacteria and fungi involves in several cases the promiscuous usage of siderophores. Thus, antibiotic resistance from these microorganisms can be circumvented through a strategy of loading toxic metals into siderophores (Trojan Horse Effect). Desferrioxamine (dfo) and its cell-permeant derivative desferrioxamine-caffeine (dfcaf) were complexed with aluminum or gallium for this purpose. The complexes Me(dfo) and Me(dfcaf) (Me = Al3+ and Ga3+) were synthesized and characterized by mass spectroscopy and cyclic voltammetry. Their relative stabilities were studied through competitive equilibria with fluorescent probes calcein, fluorescein-desferrioxamine and 8-hydroxyquinoline. Me(dfo) and Me(dfcaf) were consistently more toxic than free Me3+ against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans, demonstrating the Trojan Horse Effect. Wide spectrum antimicrobial action can be obtained by loading non-essential or toxic metal ions to microbes via a convenient siderophore carrier. (C) 2017 Elsevier GmbH. All rights reserved.
引用
收藏
页码:16 / 22
页数:7
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