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Sci Rep. 2017 Nov 15;7(1):15653. doi: 10.1038/s41598-017-15969-3.

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

Author information

1
Biophysical Immunology Laboratory, Dept. of Biomedicine, Aarhus University, Aarhus, Denmark.
2
CF and Chronic Lung Infection, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
3
Dept. of Clinical Microbiology, Aarhus University Hospital Skejby, Aarhus, Denmark.
4
Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Aarhus, Denmark.
5
Dept. of Molecular Biology & Genetics, Aarhus University, Aarhus, Denmark.
6
Dept. of Bioscience, Aarhus University, Aarhus, Denmark.
7
Dept. of Structural Biology, Max Planck Institute of Biophysics, Frankfurt, Germany.
8
Core Center for Molecular Morphology, Section for Stereology and Microscopy, Dept. of Clinical Medicine, Aarhus University, Aarhus, Denmark.
9
Center for Stochastic Geometry and Advanced Bioimaging, Aarhus University, Aarhus, Denmark.
10
Dept. of Clinical Medicine, Aarhus University, Aarhus, Denmark.
11
Dept. of Medicine, Division of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
12
Dept. of Paediatric Respiratory Medicine, Royal Brompton & Harefield Foundation Trust, London, UK.
13
Aarhus University Network for Interdisciplinary Drug Resistance Research, Aarhus, Denmark.
14
Dept. of Infectious Diseases, The Royal Hospital, Muscat, Sultanate of Oman.
15
Biophysical Immunology Laboratory, Dept. of Biomedicine, Aarhus University, Aarhus, Denmark. vorup-jensen@biomed.au.dk.
16
Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Aarhus, Denmark. vorup-jensen@biomed.au.dk.
17
Aarhus University Network for Interdisciplinary Drug Resistance Research, Aarhus, Denmark. vorup-jensen@biomed.au.dk.

Abstract

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.

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