Imaging and Treatment of Bacterial Infections with Siderophores

Antibiotic resistance is an imminent global health threat. Accelerated diagnosis and new life-saving treatments are needed to overcome resistance. Most pathogens have developed sophisticated mechanisms to sequester the essential metal ion Fe(III) from their host. This process involves Fe(III) chelators called siderophores. Naturally occurring and synthetic siderophores can act as Trojan horses to deliver antibiotics to the site of infection. These conjugates are referred to as sideromycins. We are exploring sideromycins as new therapeutic tools for the treatment of bacterial infections in combination with non-redox active metal ions that mimic Fe(III), but can further enhance bacteriotoxicity, such as Ga(III). We also employ radioactive gallium isotopes to characterize stability, bacterial uptake and in vivo pharmacokinetics of our constructs, providing unprecedented access to predicting bicompatibility and efficacy.

Representative Publication:

Cao, M., Huynh, M., Josts, I., Lao, Y., Dang, H. H., Marlin, A., Huang, X., Tidow, H., Boros, E. “Covalent Chemical Tagging of Transmembrane Transport Proteins Illuminates the Internalization Pathways of Xenosiderophores”. J. Am. Chem. Soc. 2026, 148, 20, 20509–20519.

A. Marlin, P. Tran, M. Dierolf, M. Deluca, A. Joaqui-Joaqui, O. Glaser, A. Koller, E. Alucio-Sarduy. M. Gork, D. Śmiłowicz, V. Pierre, J. W. Engle, E. Boros. “Evaluation of PSMA-targeted TREN-CAM conjugates for targeted imaging of cancer with 68Ga(III) and 45Ti(IV)”. Bioconjug. Chem., 2025, 36 (4), 859-866.

A. Koller, O. M. Glaser, M. DeLuca, R. Motz, E. Amason, I. Carbo-Bague, J. Mixdorf, I. Guzei, E. Aluicio-Sarduy, D. Śmiłowicz, T. E. Barhart, C. Ramogida, E. Nolan, J. W. Engle, E. Boros. “"Off-Label" Use of Enterobactin Enables Targeted Imaging of Cancer with Radioactive Ti(IV)” Angew. Chem. Int. Ed. 2024, e202319578

A. Pandey, M. Cao, E. Boros. Tracking Uptake and Metabolism of Xenometallomycins Using a Multi-Isotope Tagging Strategy. ACS Inf. Dis. 2022, in press.

A. Pandey, D. Śmiłowicz, E. Boros. Galbofloxacin: A Xenometal-Antibiotic with Potent in vitro and in vivo Efficacy Against S. aureus. Chem Sci. 2021, 12, 14546 - 14556. Also read about this work in C&EN News and Chemistry World.