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

TitleThe Immunomodulatory Drug Glatiramer Acetate is Also an Effective Antimicrobial Agent that Kills Gram-negative Bacteria.
Publication TypeJournal Article
Year of Publication2017
AuthorsChristiansen, SHill, Murphy, RA, Juul-Madsen, K, Fredborg, M, Hvam, MLykke, Axelgaard, E, Skovdal, SM, Meyer, RLouise, Sørensen, UBSkov, Möller, A, Nyengaard, JRandel, Nørskov-Lauritsen, N, Wang, M, Gadjeva, M, Howard, KA, Davies, JC, Petersen, E, Vorup-Jensen, T
JournalSci Rep
Volume7
Issue1
Pagination15653
Date Published2017 Nov 15
ISSN2045-2322
KeywordsAcinetobacter baumannii, Anti-Bacterial Agents, Anti-Infective Agents, Drug Resistance, Bacterial, Escherichia coli, Glatiramer Acetate, Gram-Negative Bacteria, Humans, Immunologic Factors, Methicillin-Resistant Staphylococcus aureus, Microbial Sensitivity Tests, Pseudomonas aeruginosa, Staphylococcal Infections
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.

DOI10.1038/s41598-017-15969-3
Alternate JournalSci Rep
PubMed ID29142299
PubMed Central IDPMC5688084
Grant ListR01 EY022054 / EY / NEI NIH HHS / United States