Journal
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
Volume 76, Issue 2, Pages 443-450Publisher
OXFORD UNIV PRESS
DOI: 10.1093/jac/dkaa434
Keywords
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Funding
- Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Istanbul University, Turkey
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This study evaluated the effects of ceragenins on various forms of S. maltophilia and found that CSA-131 has potential antimicrobial and antibiofilm effects, with low cytotoxicity to CF cell lines.
Background: Stenotrophomonas maltophilia is a Gram-negative bacterium resistant to several antibiotics and its prevalence in cystic fibrosis (CF) patients is increasing. Objectives: To evaluate the effects of ceragenins, non-peptide mimics of antimicrobial peptides, against both planktonic and biofilm forms of S. maltophilia and the cytotoxicity of ceragenins to the IB3-1 CF cell line. Methods: Ceragenin CSA-131, with and without 5% Pluronic (R) F127 (a non-ionic amphiphilic poloxamer), and ceragenin CSA-13 were evaluated against S. maltophilia clinical isolates (n = 40). MICs and MBCs of ceragenins and conventional antibiotics were determined. Time-kill curve experiments were performed with 1x, 2x and 4x MICs of ceragenins. The highest non-cytotoxic concentrations of ceragenins against IB3-1, a CF cell line, were determined by MTT assay. The effects of ceragenins against biofilm adhesion, formation and mature biofilms were investigated. Results: CSA-131 with Pluronic (R) F127 displayed the lowest MICs (MIC50/MIC90: 1/2 mg/L) followed by CSA-131 (MIC50/MIC90: 2/4 mg/L), while those of CSA-13 were much higher (MIC50/MIC90: 16/32 mg/L). According to time-kill curve results, all concentrations at 4% MICs of ceragenins showed bactericidal activity (3 log reduction) after 4 h. While CSA-131 and CSA-131-poloxamer inhibited biofilm adhesion and formation by 87.74% and 83.42%, respectively, after 24 h, CSA-131 was more effective on mature biofilms. Formulating CSA-131 in poloxamer micelles did not affect the cytotoxicity of CSA-131 to IB3-1 cells. Conclusions: CSA-131 could be a potential antimicrobial agent for the treatment of S. maltophilia infections in CF, due to its low cytotoxicity on the CF cell line and good antimicrobial and antibiofilm effects.
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