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J Trace Elem Med Biol ; 41: 16-22, 2017 May.
Article in English | MEDLINE | ID: mdl-28347458

ABSTRACT

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.


Subject(s)
Aluminum/pharmacology , Anti-Bacterial Agents/pharmacology , Antioxidants/pharmacology , Caffeine/pharmacology , Deferoxamine/pharmacology , Gallium/pharmacology , Aluminum/chemistry , Anti-Bacterial Agents/chemistry , Antioxidants/chemistry , Caffeine/chemistry , Candida albicans/drug effects , Deferoxamine/chemistry , Dose-Response Relationship, Drug , Drug Carriers/chemistry , Drug Carriers/pharmacology , Escherichia coli/drug effects , Gallium/chemistry , Microbial Sensitivity Tests , Pseudomonas aeruginosa/drug effects , Staphylococcus aureus/drug effects
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