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Silver coordination polymers for prevention of implant infection: thiol interaction, impact on respiratory chain enzymes, and hydroxyl radical induction

  • Gordon, Oliver Infection Biology, Department of Biomedicine, University Hospital, Basel, Switzerland
  • Slenters, Tünde Vig University of Fribourg, Department of Chemistry, Switzerland - University of Basel, Department of Chemistry, Switzerland
  • Brunetto, Priscilla S. University of Fribourg, Department of Chemistry, Switzerland
  • Villaruz, Amer E. National Institute of Allergy and Infectious Diseases, The National Institutes of Health, Bethesda, USA
  • Sturdevant, Daniel E. Research Technologies Branch, Genomics Unit, Rocky Mountain Laboratories, Hamilton, Montana, USA
  • Otto, Michael National Institute of Allergy and Infectious Diseases, The National Institutes of Health, Bethesda, USA
  • Landmann, Regine Infection Biology, Department of Biomedicine, University Hospital, Basel, Switzerland
  • Fromm, Katharina M. University of Fribourg, Department of Chemistry, Switzerland
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    26.07.2010
Published in:
  • Antimicrobial Agents and Chemotherapy. - 2010, vol. 54, no. 10, p. 4208-4218
English Prosthetic joint replacements are used increasingly to alleviate pain and improve mobility of the progressively older and more obese population. Implant infection occurs in about 5% of patients and entails significant morbidity and high social costs. It is most often caused by staphylococci, which are introduced perioperatively. They are a source of prolonged seeding and difficult to treat due to antibiotic resistance; therefore, infection prevention by prosthesis coating with nonantibiotic-type anti- infective substances is indicated. A renewed interest in topically used silver has fostered development of silver nanoparticles, which, however, present a potential health hazard. Here we present new silver coordination polymer networks with tailored physical and chemical properties as nanostructured coatings on metallic implant substrates. These compounds exhibited strong biofilm sugar-independent bactericidal activity on in vitro-grown biofilms and prevented murine Staphylococcus epidermidis implant infection in vivo with slow release of silver ions and limited transient leukocyte cytotoxicity. Furthermore, we describe the biochemical and molecular mechanisms of silver ion action by gene screening and by targeting cell metabolism of S. epidermidis at different levels. We demonstrate that silver ions inactivate enzymes by binding sulfhydryl (thiol) groups in amino acids and promote the release of iron with subsequent hydroxyl radical formation by an indirect mechanism likely mediated by reactive oxygen species. This is the first report investigating the global metabolic effects of silver in the context of a therapeutic application. We anticipate that the compounds presented here open a new treatment field with a high medical impact.
Faculty
Faculté des sciences et de médecine
Department
Département de Chimie
Language
  • English
Classification
Chemistry
License
License undefined
Identifiers
Persistent URL
https://folia.unifr.ch/unifr/documents/301776
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