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Multivalent Siderophore–DOTAM Conjugates as Theranostics for Imaging and Treatment of Bacterial Infections |
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| Authors: | M?Sc Kevin Ferreira Dr Hai-Yu Hu Dr Verena Fetz Dr Hans Prochnow Dr Bushra Rais Prof?Dr Peter P Müller Prof?Dr Mark Brönstrup |
| Affiliation: | 1. Department of Chemical Biology, Helmholtz Centre for Infection Research and German Centre for Infection Research (DZIF), Inhoffenstrasse 7, 38124 Braunschweig, Germany
These authors contributed equally to this work.;2. Department of Chemical Biology, Helmholtz Centre for Infection Research and German Centre for Infection Research (DZIF), Inhoffenstrasse 7, 38124 Braunschweig, Germany State Key Laboratory of Bioactive Substances and Function of Natural Medicine, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Xiannongtan Street, 100050 P.R. China These authors contributed equally to this work.;3. Department of Chemical Biology, Helmholtz Centre for Infection Research and German Centre for Infection Research (DZIF), Inhoffenstrasse 7, 38124 Braunschweig, Germany School of Engineering and Science, Jacobs University Bremen, Germany These authors contributed equally to this work.;4. Department of Chemical Biology, Helmholtz Centre for Infection Research and German Centre for Infection Research (DZIF), Inhoffenstrasse 7, 38124 Braunschweig, Germany |
| Abstract: | There is a strong need to better diagnose infections at deep body sites through noninvasive molecular imaging methods. Herein, we describe the synthesis and characterization of probes based on siderophore conjugates with catechol moieties and a central DOTAM scaffold. The probes can accommodate a metal ion as well as an antibiotic moiety and are therefore suited for theranostic purposes. The translocation of the conjugates across the outer and inner cell membranes of E. coli was confirmed by growth recovery experiments with enterobactin-deficient strains, by the antibacterial activity of ampicillin conjugates, and by confocal imaging using a fluorogen-activating protein–malachite green system adapted to E. coli. The suitability of the probes for in vivo imaging was demonstrated with a Cy5.5 conjugate in mice infected with P. aeruginosa. |
| Keywords: | antibiotics drug conjugates drug delivery imaging siderophores |
