Th IV -Desferrioxamine: characterization of a fluorescent bacterial probe

Diversifying our ability to guard against emerging pathogenic threats is essential for keeping pace with global health challenges, including those presented by drug-resistant bacteria. Some modern diagnostic and therapeutic innovations to address this challenge focus on targeting methods that exploit bacterial nutrient sequestration pathways, such as the desferrioxamine (DFO) siderophore used by ( ) to sequester Fe . Building on recent studies that have shown DFO to be a versatile vehicle for chemical delivery, we show proof-of-principle that the Fe sequestration pathway can be used to deliver a potential radiotherapeutic. Our approach replaces the Fe nutrient sequestered by H DFO with Th and made use of a common fluorophore, FITC, which we covalently bonded to DFO to provide a combinatorial probe for simultaneous chelation paired with imaging and spectroscopy, H DFO_FITC. Combining insight provided from FITC-based imaging with characterization by NMR spectroscopy, we demonstrated that the fluorescent DFO_FITC conjugate retained the Th chelation properties of native H DFO . Fluorescence microscopy with both [Th(DFO_FITC)] and [Fe(DFO_FITC)] complexes showed similar uptake by and increased intercellular accumulation as compared to the FITC and unchelated H DFO_FITC controls. Collectively, these results demonstrate the potential for the newly developed H DFO_FITC conjugate to be used as a targeting vector and bacterial imaging probe for . The results presented within provide a framework to expand H DFO and H DFO_FITC to relevant radiotherapeutics (like Th).