Özlem Oyardi1, Paul B Savage2, Zayre Erturan3, Cagla Bozkurt-Guzel1. 1. Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Istanbul University, 34116, Istanbul, Turkey. 2. Department of Chemistry and Biochemistry, Brigham Young University, 84602, Provo, UT, USA. 3. Department of Medical Microbiology, Faculty of Medicine, Istanbul University, 34093, Istanbul, Turkey.
Abstract
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® 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 1×, 2× and 4× 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® 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.
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® 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 1×, 2× and 4× 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® 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.
Authors: Paulina Paprocka; Angelika Mańkowska; Karol Skłodowski; Grzegorz Król; Tomasz Wollny; Agata Lesiak; Katarzyna Głuszek; Paul B Savage; Bonita Durnaś; Robert Bucki Journal: Pathogens Date: 2022-05-26