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

The Immunomodulatory Drug Glatiramer Acetate is Also an Effective Antimicrobial Agent that Kills Gram-negative Bacteria.
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Christiansen SH, Murphy RA, Juul-Madsen K, Fredborg M, Hvam ML, Axelgaard E, Skovdal SM, Meyer RL, Sørensen UBS, Möller A, Nyengaard JR, Nørskov-Lauritsen N, Wang M, Gadjeva M, Howard KA, Davies JC, Petersen E, Vorup-Jensen T,


Christiansen SH, Murphy RA, Juul-Madsen K, Fredborg M, Hvam ML, Axelgaard E, Skovdal SM, Meyer RL, Sørensen UBS, Möller A, Nyengaard JR, Nørskov-Lauritsen N, Wang M, Gadjeva M, Howard KA, Davies JC, Petersen E, Vorup-Jensen T, (click to view)

Christiansen SH, Murphy RA, Juul-Madsen K, Fredborg M, Hvam ML, Axelgaard E, Skovdal SM, Meyer RL, Sørensen UBS, Möller A, Nyengaard JR, Nørskov-Lauritsen N, Wang M, Gadjeva M, Howard KA, Davies JC, Petersen E, Vorup-Jensen T,

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Scientific reports 2017 11 157(1) 15653 doi 10.1038/s41598-017-15969-3
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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