Th-Desferrioxamine: characterization of a fluorescent bacterial probe

• Published in: Dalton transactions : an international journal of inorganic chemistry Vol. 5; no. 42; pp. 1531 - 1532
• Main Authors: Aldrich, Kelly Elise, Livshits, Maksim Yuryevich, Stromberg, Loreen Rose, Janicke, Michael Timothy, Nhu Lam, Mila, Stein, Benjamin, Wagner, Gregory Lawerence, Abergel, Rebecca J, Mukundan, Harshini, Kozimor, Stosh Anthony, Lilley, Laura Margaret
• Format: Journal Article
• Published: 14.11.2021
• ISSN: 1477-9226; 1477-9234
• DOI: 10.1039/d1dt02177j

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 Staphylococcus aureus ( S. aureus ) to sequester Fe III . Building on recent studies that have shown DFO to be a versatile vehicle for chemical delivery, we show proof-of-principle that the Fe III sequestration pathway can be used to deliver a potential radiotherapeutic. Our approach replaces the Fe III nutrient sequestered by H 4 DFO + with Th IV 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 3 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 IV chelation properties of native H 4 DFO + . Fluorescence microscopy with both [Th(DFO_FITC)] and [Fe(DFO_FITC)] complexes showed similar uptake by S. aureus and increased intercellular accumulation as compared to the FITC and unchelated H 3 DFO_FITC controls. Collectively, these results demonstrate the potential for the newly developed H 3 DFO_FITC conjugate to be used as a targeting vector and bacterial imaging probe for S. aureus . The results presented within provide a framework to expand H 4 DFO + and H 3 DFO_FITC to relevant radiotherapeutics (like 227 Th). Here we present the solution state structure of thorium( iv ) desferrioxamine (DFO), a bacterial siderophore, and a synthesized fluorescent conjugate amenable for bacterial imaging.