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

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

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Title: The Immunomodulatory Drug Glatiramer Acetate is Also an Effective Antimicrobial Agent that Kills Gram-negative Bacteria
Author: Christiansen, Stig Hill; Murphy, Ronan A.; Juul-Madsen, Kristian; Fredborg, Marlene; Hvam, Michael Lykke; Axelgaard, Esben; Skovdal, Sandra M.; Meyer, Rikke Louise; Sørensen, Uffe B. Skov; Möller, Arne; Nyengaard, Jens Randel; Nørskov-Lauritsen, Niels; Wang, Mikala; Gadjeva, Mihaela; Howard, Kenneth A.; Davies, Jane C.; Petersen, Eskild; Vorup-Jensen, Thomas

Note: Order does not necessarily reflect citation order of authors.

Citation: Christiansen, S. H., R. A. Murphy, K. Juul-Madsen, M. Fredborg, M. L. Hvam, E. Axelgaard, S. M. Skovdal, et al. 2017. “The Immunomodulatory Drug Glatiramer Acetate is Also an Effective Antimicrobial Agent that Kills Gram-negative Bacteria.” Scientific Reports 7 (1): 15653. doi:10.1038/s41598-017-15969-3. http://dx.doi.org/10.1038/s41598-017-15969-3.
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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.
Published Version: doi:10.1038/s41598-017-15969-3
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5688084/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:34493160
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