1. The Immunomodulatory Drug Glatiramer Acetate is Also an Effective Antimicrobial Agent that Kills Gram-negative Bacteria
- Author
-
Thomas Vorup-Jensen, Marlene Fredborg, Michael Lykke Hvam, Rikke Louise Meyer, R.A. Murphy, Mihaela Gadjeva, Jens R. Nyengaard, Arne Möller, Stig Hill Christiansen, M. Wang, Sandra M. Skovdal, Kenneth A. Howard, Eskild Petersen, Jane C. Davies, Kristian Juul-Madsen, Uffe B. Skov Sørensen, Esben Axelgaard, and Niels Nørskov-Lauritsen
- Subjects
Acinetobacter baumannii ,0301 basic medicine ,Antibiotics ,lcsh:Medicine ,Immunologic Factors/pharmacology ,Staphylococcal Infections/drug therapy ,Drug resistance ,medicine.disease_cause ,MOLECULES ,Anti-Infective Agents ,lcsh:Science ,Methicillin-Resistant Staphylococcus aureus/drug effects ,Escherichia coli/drug effects ,Multidisciplinary ,biology ,Chemistry ,PEPTIDES ,Drug Resistance, Bacterial/genetics ,MULTIPLE-SCLEROSIS ,Staphylococcal Infections ,Antimicrobial ,Anti-Bacterial Agents ,TARGET ,INFECTIONS ,Staphylococcus aureus ,Glatiramer Acetate/pharmacology ,Pseudomonas aeruginosa ,Gram-Negative Bacteria/drug effects ,ANTIBIOTICS ,Methicillin-Resistant Staphylococcus aureus ,Gram-negative bacteria ,medicine.drug_class ,Antimicrobial peptides ,Microbial Sensitivity Tests ,Article ,Pseudomonas aeruginosa/drug effects ,Anti-Bacterial Agents/pharmacology ,Microbiology ,03 medical and health sciences ,Drug Resistance, Bacterial ,Gram-Negative Bacteria ,Escherichia coli ,medicine ,Immunologic Factors ,Humans ,ATOMIC-FORCE MICROSCOPY ,STAPHYLOCOCCUS-AUREUS ,lcsh:R ,Anti-Infective Agents/chemistry ,Glatiramer Acetate ,biology.organism_classification ,030104 developmental biology ,CELLS ,lcsh:Q ,Acinetobacter baumannii/drug effects ,RESISTANCE - 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
- 2017