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The Immunomodulatory Drug Glatiramer Acetate is Also an Effective Antimicrobial Agent that Kills Gram-negative Bacteria
- Source :
- Hill Christiansen, S, Murphy, R A, Juul-Madsen, K, Fredborg, M, Hvam, M L, Axelgaard, E, Skovdal, S M, Meyer, R L, Sørensen, U B S, Möller, A, Nyengaard, J R, Nørskov-Lauritsen, N, Wang, M, Gadjeva, M, Howard, K A, Davies, J C, Petersen, E & Vorup-Jensen, T 2017, ' The Immunomodulatory Drug Glatiramer Acetate is Also an Effective Antimicrobial Agent that Kills Gram-negative Bacteria ', Scientific Reports, vol. 7, 15653 . https://doi.org/10.1038/s41598-017-15969-3, Christiansen, S H, Murphy, R A, Juul-Madsen, K, Fredborg, M, Hvam, M L, Axelgaard, E, Skovdal, S M, Meyer, R L, Sorensen, U B S, Moeller, A, Nyengaard, J R, Norskov-Lauritsen, N, Wang, M, Gadjeva, M, Howard, K A, Davies, J C, Petersen, E & Vorup-Jensen, T 2017, ' The Immunomodulatory Drug Glatiramer Acetate is Also an Effective Antimicrobial Agent that Kills Gram-negative Bacteria ', Scientific Reports, vol. 7, 15653 . https://doi.org/10.1038/s41598-017-15969-3, Scientific Reports, Vol 7, Iss 1, Pp 1-16 (2017), Scientific Reports
- Publication Year :
- 2017
- Publisher :
- Springer Science and Business Media LLC, 2017.
-
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.
- 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
Subjects
Details
- ISSN :
- 20452322
- Volume :
- 7
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....f99382febee1c7502b41664ee0b7018f