title: Desferrioxamine and desferrioxamine-caffeine as carriers of aluminum and gallium to microbes via the Trojan Horse Effect.
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.
authors.affiliation: Department of Fundamental Chemistry, Institute of Chemistry, University of São Paulo,Av. Prof. Lineu Prestes, 748, 05508-000, São Paulo, SP, Brazil.
authors.forename: Jesus Antonio Alvarado
authors.initials: JAA
authors.lastname: Huayhuaz
authors.affiliation: Department of Fundamental Chemistry, Institute of Chemistry, University of São Paulo,Av. Prof. Lineu Prestes, 748, 05508-000, São Paulo, SP, Brazil.
authors.forename: Hector Aguilar
authors.initials: HA
authors.lastname: Vitorino
authors.affiliation: Department of Fundamental Chemistry, Institute of Chemistry, University of São Paulo,Av. Prof. Lineu Prestes, 748, 05508-000, São Paulo, SP, Brazil.
authors.forename: Othon Souto
authors.initials: OS
authors.lastname: Campos
authors.affiliation: Department of Fundamental Chemistry, Institute of Chemistry, University of São Paulo,Av. Prof. Lineu Prestes, 748, 05508-000, São Paulo, SP, Brazil.
authors.forename: Silvia Helena Pires
authors.initials: SHP
authors.lastname: Serrano
authors.affiliation: Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Telma Mary
authors.initials: TM
authors.lastname: Kaneko
authors.affiliation: Department of Fundamental Chemistry, Institute of Chemistry, University of São Paulo,Av. Prof. Lineu Prestes, 748, 05508-000, São Paulo, SP, Brazil. Electronic address: breno@iq.usp.br.
authors.forename: Breno Pannia
authors.initials: BP
authors.lastname: Espósito
mesh_terms: D000535:Aluminum / Q000737:chemistry / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D002110:Caffeine / Q000737:chemistry / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects; D003676:Deferoxamine / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000737:chemistry / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects; D005708:Gallium / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D000975:Antioxidants; D004337:Drug Carriers; D002110:Caffeine; D005708:Gallium; D000535:Aluminum; D003676:Deferoxamine
keywords: Aluminum; Caffeine; Desferrioxamine; Gallium; Trojan horse