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The Immunomodulatory Drug Glatiramer Acetate is Also an Effective Antimicrobial Agent that Kills Gram-negative Bacteria

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  • Stig Hill Christiansen
  • ,
  • Ronan A. Murphy, Imperial College London
  • ,
  • Kristian Juul-Madsen
  • Marlene Fredborg, Aarhus Universitets Hospital, Skejby
  • ,
  • Michael Lykke Hvam
  • ,
  • Esben Axelgaard
  • Sandra M. Skovdal
  • ,
  • Rikke Louise Meyer
  • Uffe B. Skov Sorensen
  • ,
  • Arne Moeller, Max Planck Institute of Biophysics
  • ,
  • Jens Randel Nyengaard
  • Niels Norskov-Lauritsen, Aarhus Universitets Hospital, Skejby
  • ,
  • Mikala Wang
  • Mihaela Gadjeva, Harvard University
  • ,
  • Kenneth A. Howard
  • Jane C. Davies, Royal Brompton & Harefield Foundation Trust, Imperial College London
  • ,
  • Eskild Petersen, The Royal Hospital, Muscat, Aarhus University Network for Interdisciplinary Drug Resistance Research
  • ,
  • Thomas Vorup-Jensen

Classic drug development strategies have failed to meet the urgent clinical needs in treating infections with Gram-negative bacteria. Repurposing drugs can lead to timely availability of new antibiotics, accelerated by existing safety profiles. Glatiramer acetate (GA) is a widely used and safe formulation for treatment of multiple sclerosis. It contains a large diversity of essentially isomeric polypeptides with the cationic and amphiphilic character of many antimicrobial peptides (AMP). Here, we report that GA is antibacterial, targeting Gram-negative organisms with higher activity towards Pseudomonas aeruginosa than the naturally-occurring AMP LL-37 in human plasma. As judged from flow cytometric assays, bacterial killing by GA occurred within minutes. Laboratory strains of Escherichia coli and P. aeruginosa were killed by a process of condensing intracellular contents. Efficient killing by GA was also demonstrated in Acinetobacter baumannii clinical isolates and approximately 50% of clinical isolates of P. aeruginosa from chronic airway infection in CF patients. By contrast, the Gram-positive Staphylococcus aureus cells appeared to be protected from GA by an increased formation of nm-scale particulates. Our data identify GA as an attractive drug repurposing candidate to treat infections with Gram-negative bacteria.

Original languageEnglish
Article number15653
JournalScientific Reports
Number of pages16
Publication statusPublished - 15 Nov 2017

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