Oral Presentation 21st International Conference on Biological Inorganic Chemistry 2025

Harnessing Artificial Siderophores for Targeting Pathogens and Advancing Molecular Imaging (121978)

Elzbieta Gumienna-Kontecka 1 , Klaudia Szczerba 1 , Hubertus Haas 2 , Milos Petrik 3 , Clemens Decristoforo 4 , Isabelle Schalk 5 , Henryk Kozlowski 1 , Elzbieta Wojaczynska 6
  1. University of Wroclaw, Wroclaw, Poland
  2. Department of Molecular Biology, Medical University of Innsbruck, Innsbruck, Austria
  3. Institute of Molecular and Translational Medicine, Palacký University Olomouc, Olomouc, Czech Republic
  4. Department of Nuclear Medicine, Medical University of Innsbruck, Innsbruck, Austria
  5. CNRS, UMR7242, ESBS, University of Strasbourg, Strasbourg, France
  6. Faculty of Chemistry, Wrocław University of Science and Technology, Wroclaw, Poland

Under iron-deficient conditions most aerobic microorganisms secret low molecular-weight chelating compounds – siderophores, which actively transport ferric ions into the cells via specific transporters in the microbial membranes [1, 2]. The difficulties in synthesis of structurally complicated natural siderophores has directed us towards biomimetic chemistry, aiming at mimicking or reproducing the function of the natural product rather than its detailed structure. This approach allowed us to diversify the arsenal of biologically active siderophore-type molecules, introduce additional desired chemical and/or physical properties, and provide means to identify general motifs governing an interplay between structure and function in biological activity [1-5].

Taking into account, that siderophores are absent in the host cells, they are tempting targets for microbial imaging, for example with 68Ga or 89Zr using positron emission tomography (PET) [6]. Of the evaluated siderophores, 68Ga-ferrioxamine E and its close biomimetic analogues were shown as the most promising for possible applications in PET imaging of S. aureus and A. fumigatus species [5, 7]. Currently we are working on other bacterial (P. aeruginosa) and fungal species, to better understand the in vivo speciation and differences in the biological recognition and uptake of these artificial siderophores.

Overall, mimics of siderophores may hold potential as inert and stable carriers for Fe(III), Ga(III) and Zr(IV) ions for diagnostic medical applications. They could also allow identifying critical microbial compartments in which siderophores accumulate and thus illuminate key targets for specific drugs against microbial diseases.

Acknowledgements
The research has received funding from Polish National Science Centre (UMO-2022/47/I/ST4/02354 and UMO-2017/26/A/ST5/00363).

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