title: Enhancement of antibiotic-activity through complexation with metal ions - Combined ITC, NMR, enzymatic and biological studies.
abstract: Alternative solutions need to be developed to overcome the growing problem of multi-drug resistant bacteria. This study explored the possibility of creating complexes of antibiotics with metal ions, thereby increasing their activity. Analytical techniques such as isothermal titration calorimetry and nuclear magnetic resonance were used to examine the structure and interactions between Cu(II), Ag(I) or Zn(II) and β-lactam antibiotics. The metal-β-lactam complexes were also tested for antimicrobial activity, by micro-broth dilution and disk diffusion methods, showing a synergistic increase in the activity of the drugs, and enzymatic inhibition assays confirming inhibition of β-lactamases responsible for resistance. The metal-antibiotic complex concept was proven to be successful with the activity of the drugs enhanced against β-lactamase-producing bacteria. The highest synergistic effects were observed for complexes formed with Ag(I).
authors.affiliation: The University of Queensland, School of Chemistry and Molecular Biosciences, St Lucia 4072, Australia.
authors.forename: Jasper S
authors.initials: JS
authors.lastname: Möhler
authors.affiliation: The University of Queensland, School of Chemistry and Molecular Biosciences, St Lucia 4072, Australia.
authors.forename: Theresa
authors.initials: T
authors.lastname: Kolmar
authors.affiliation: The University of Queensland, School of Chemistry and Molecular Biosciences, St Lucia 4072, Australia.
authors.forename: Kevin
authors.initials: K
authors.lastname: Synnatschke
authors.affiliation: The University of Queensland, School of Chemistry and Molecular Biosciences, St Lucia 4072, Australia.
authors.forename: Marcel
authors.initials: M
authors.lastname: Hergert
authors.affiliation: The University of Queensland, School of Chemistry and Molecular Biosciences, St Lucia 4072, Australia.
authors.forename: Liam A
authors.initials: LA
authors.lastname: Wilson
authors.affiliation: The University of Queensland, Institute for Molecular Bioscience, St Lucia 4072, Australia.
authors.forename: Soumya
authors.initials: S
authors.lastname: Ramu
authors.affiliation: The University of Queensland, Institute for Molecular Bioscience, St Lucia 4072, Australia.
authors.forename: Alysha G
authors.initials: AG
authors.lastname: Elliott
authors.affiliation: The University of Queensland, Institute for Molecular Bioscience, St Lucia 4072, Australia.
authors.forename: Mark A T
authors.initials: MA
authors.lastname: Blaskovich
authors.affiliation: The University of Queensland, UQ Centre for Clinical Research, Royal Brisbane and Women's Hospital, Brisbane, Queensland 4029, Australia.
authors.forename: Hanna E
authors.initials: HE
authors.lastname: Sidjabat
authors.affiliation: The University of Queensland, UQ Centre for Clinical Research, Royal Brisbane and Women's Hospital, Brisbane, Queensland 4029, Australia.
authors.forename: David L
authors.initials: DL
authors.lastname: Paterson
authors.affiliation: The University of Queensland, School of Chemistry and Molecular Biosciences, St Lucia 4072, Australia.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Schenk
authors.affiliation: The University of Queensland, Institute for Molecular Bioscience, St Lucia 4072, Australia.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Cooper
authors.affiliation: The University of Queensland, Institute for Molecular Bioscience, St Lucia 4072, Australia. Electronic address: z.ziora@uq.edu.au.
authors.forename: Zyta M
authors.initials: ZM
authors.lastname: Ziora
mesh_terms: D001419:Bacteria / Q000201:enzymology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D019216:Metals, Heavy; D065093:beta-Lactamase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D001618:beta-Lactamases / Q000378:metabolism*; D047090:beta-Lactams / Q000737:chemistry / Q000494:pharmacology
chemical_list: D001426:Bacterial Proteins; D019216:Metals, Heavy; D065093:beta-Lactamase Inhibitors; D047090:beta-Lactams; D001618:beta-Lactamases
keywords: Metal-antibiotic complexes; Multi-drug resistant bacteria; Synergism; β-Lactam antibiotic; β-Lactamases