Abstract
Antibiotics that are normally used to treat infections caused by Gram-positive bacteria might be made effective against Gram-negative bacterial infections, if they can circumvent permeability barriers and antibiotic deactivation processes associated with Gram-negative bacteria. Herein we report syntheses of bis-catechol–teicoplanin and mixed ligand catechol–hydroxamate–teicoplanin conjugates. Antibacterial activity assays revealed that conjugation of teicoplanin, which is only known to be active against Gram-positive bacteria, to the siderophore mimics induced potent activity against multidrug resistant strains of select Gram-negative bacteria (Acinetobacter baumannii) while retaining moderate activity against Gram-positive bacteria (Staphylococcus aureus).
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Acknowledgements
We thank Hsiri Therapeutics for support of this research and B. Boggess and N. Sevov at the University of Notre Dame for LC/MS assistance and the University of Notre Dame NMR facility.
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The authors are employees of Hsiri Therapeutics and claim no other conflict of interest.
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Supplemental Material: Antibiotic Repurposing: Bis-catechol- and Mixed Ligand (Bis-catechol-mono-hydroxamate)-Teicoplanin Conjugates are Active against Multi-Drug Resistant Acinetobacter baumannii
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Ghosh, M., Miller, P.A. & Miller, M.J. Antibiotic repurposing: bis-catechol- and mixed ligand (bis-catechol-mono-hydroxamate)-teicoplanin conjugates are active against multidrug resistant Acinetobacter baumannii. J Antibiot 73, 152–157 (2020). https://doi.org/10.1038/s41429-019-0268-7
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DOI: https://doi.org/10.1038/s41429-019-0268-7
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