Huayhuaz Jesus Antonio Alvarado, Vitorino Hector Aguilar, Campos Othon Souto, Serrano Silvia Helena Pires, Kaneko Telma Mary, Espósito Breno Pannia
Department of Fundamental Chemistry, Institute of Chemistry, University of São Paulo,Av. Prof. Lineu Prestes, 748, 05508-000, São Paulo, SP, Brazil.
Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, SP, Brazil.
J Trace Elem Med Biol. 2017 May;41:16-22. doi: 10.1016/j.jtemb.2017.01.006. Epub 2017 Feb 3.
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=Al and Ga) 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 Me 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.
细菌和真菌获取铁的过程在某些情况下涉及到铁载体的随意使用。因此，通过将有毒金属加载到铁载体中的策略（特洛伊木马效应），可以规避这些微生物的抗生素耐药性。为此，去铁胺（dfo）及其可穿透细胞的衍生物去铁胺 - 咖啡因（dfcaf）与铝或镓形成了络合物。合成了络合物Me(dfo)和Me(dfcaf)（Me = Al和Ga），并通过质谱和循环伏安法对其进行了表征。通过与荧光探针钙黄绿素、荧光素 - 去铁胺和8 - 羟基喹啉的竞争平衡研究了它们的相对稳定性。Me(dfo)和Me(dfcaf)对大肠杆菌、铜绿假单胞菌、金黄色葡萄球菌和白色念珠菌的毒性始终比游离的Me更高，证明了特洛伊木马效应。通过方便的铁载体将非必需或有毒金属离子加载到微生物上，可以获得广谱抗菌作用。
