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SH Christiansen, RA Murphy, K Juul-Madsen, M Fredborg, ML Hvam, E Axelgaard, SM Skovdal, RL Meyer, UBS Sørensen, A Möller, JR Nyengaard, N Nørskov-Lauritsen, M Wang, M Gadjeva, KA Howard, JC Davies, E Petersen and T Vorup-Jensen
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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Concepts
Pseudomonas aeruginosa, Gram-negative bacteria, Gram negative bacteria, Immune system, Escherichia coli, Microbiology, Antibiotic resistance, Bacteria
MeSH headings
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