Antimicrobial Activity of Ceragenins against Vancomycin-Susceptible and -Resistant <i>Enterococcus</i> spp.
Ceragenins (CSAs) are a new class of antimicrobial agents designed to mimic the activities of endogenous antimicrobial peptides. In this study, the antibacterial activities of various ceragenins (CSA-13, CSA-44, CSA-90, CSA-131, CSA-138, CSA-142, and CSA-192), linezolid, and daptomycin were assessed...
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| Format: | Article |
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MDPI AG
2023-11-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/16/12/1643 |
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| author | Mayram Hacioglu Fatima Nur Yilmaz Ozlem Oyardi Cagla Bozkurt Guzel Nese Inan Paul B. Savage Sibel Dosler |
| author_facet | Mayram Hacioglu Fatima Nur Yilmaz Ozlem Oyardi Cagla Bozkurt Guzel Nese Inan Paul B. Savage Sibel Dosler |
| author_sort | Mayram Hacioglu |
| collection | DOAJ |
| description | Ceragenins (CSAs) are a new class of antimicrobial agents designed to mimic the activities of endogenous antimicrobial peptides. In this study, the antibacterial activities of various ceragenins (CSA-13, CSA-44, CSA-90, CSA-131, CSA-138, CSA-142, and CSA-192), linezolid, and daptomycin were assessed against 50 non-repeated <i>Enterococcus</i> spp. (17 of them vancomycin-resistant Enterococcus-VRE) isolated from various clinical specimens. Among the ceragenins evaluated, the MIC<sub>50</sub> and MIC<sub>90</sub> values of CSA-44 and CSA-192 were the lowest (2 and 4 μg/mL, respectively), and further studies were continued with these two ceragenins. Potential interactions between CSA-44 or CSA-192 and linezolid were tested and synergistic interactions were seen with the CSA-192-linezolid combination against three <i>Enterococcus</i> spp., one of them VRE. The effects of CSA-44 and CSA-192 on the MIC values of vancomycin were also investigated, and the largest MIC change was seen in the vancomycin-CSA-192 combination. The in vivo effects of CSA-44 and CSA-192 were evaluated in a <i>Caenorhabditis elegans</i> model system. Compared to no treatment, increased survival was observed with <i>C. elegans</i> when treated with ceragenins. In conclusion, CSA-44 and CSA-192 appear to be good candidates (alone or in combination) for the treatment of enterococcal infections, including those from VRE. |
| first_indexed | 2024-03-08T20:27:11Z |
| format | Article |
| id | doaj.art-9a2cbc17bd8b43d5a7144bfe56318264 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-08T20:27:11Z |
| publishDate | 2023-11-01 |
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| series | Pharmaceuticals |
| spelling | doaj.art-9a2cbc17bd8b43d5a7144bfe563182642023-12-22T14:31:17ZengMDPI AGPharmaceuticals1424-82472023-11-011612164310.3390/ph16121643Antimicrobial Activity of Ceragenins against Vancomycin-Susceptible and -Resistant <i>Enterococcus</i> spp.Mayram Hacioglu0Fatima Nur Yilmaz1Ozlem Oyardi2Cagla Bozkurt Guzel3Nese Inan4Paul B. Savage5Sibel Dosler6Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Istanbul University, Istanbul 34116, TurkeyDepartment of Pharmaceutical Microbiology, Faculty of Pharmacy, Istanbul University, Istanbul 34116, TurkeyDepartment of Pharmaceutical Microbiology, Faculty of Pharmacy, Gazi University, Ankara 06330, TurkeyDepartment of Pharmaceutical Microbiology, Faculty of Pharmacy, Istanbul University, Istanbul 34116, TurkeyMedical Microbiology Laboratory, Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital, University of Health Sciences Ankara, Ankara 06200, TurkeyDepartment of Chemistry and Biochemistry, Brigham Young University, Provo, UT 84602, USADepartment of Pharmaceutical Microbiology, Faculty of Pharmacy, Istanbul University, Istanbul 34116, TurkeyCeragenins (CSAs) are a new class of antimicrobial agents designed to mimic the activities of endogenous antimicrobial peptides. In this study, the antibacterial activities of various ceragenins (CSA-13, CSA-44, CSA-90, CSA-131, CSA-138, CSA-142, and CSA-192), linezolid, and daptomycin were assessed against 50 non-repeated <i>Enterococcus</i> spp. (17 of them vancomycin-resistant Enterococcus-VRE) isolated from various clinical specimens. Among the ceragenins evaluated, the MIC<sub>50</sub> and MIC<sub>90</sub> values of CSA-44 and CSA-192 were the lowest (2 and 4 μg/mL, respectively), and further studies were continued with these two ceragenins. Potential interactions between CSA-44 or CSA-192 and linezolid were tested and synergistic interactions were seen with the CSA-192-linezolid combination against three <i>Enterococcus</i> spp., one of them VRE. The effects of CSA-44 and CSA-192 on the MIC values of vancomycin were also investigated, and the largest MIC change was seen in the vancomycin-CSA-192 combination. The in vivo effects of CSA-44 and CSA-192 were evaluated in a <i>Caenorhabditis elegans</i> model system. Compared to no treatment, increased survival was observed with <i>C. elegans</i> when treated with ceragenins. In conclusion, CSA-44 and CSA-192 appear to be good candidates (alone or in combination) for the treatment of enterococcal infections, including those from VRE.https://www.mdpi.com/1424-8247/16/12/1643<i>Enterococcus</i> spp.cerageninlinezolidminimum inhibitory concentrationmicrobroth checkerboard<i>Caenorhabditis elegans</i> |
| spellingShingle | Mayram Hacioglu Fatima Nur Yilmaz Ozlem Oyardi Cagla Bozkurt Guzel Nese Inan Paul B. Savage Sibel Dosler Antimicrobial Activity of Ceragenins against Vancomycin-Susceptible and -Resistant <i>Enterococcus</i> spp. Pharmaceuticals <i>Enterococcus</i> spp. ceragenin linezolid minimum inhibitory concentration microbroth checkerboard <i>Caenorhabditis elegans</i> |
| title | Antimicrobial Activity of Ceragenins against Vancomycin-Susceptible and -Resistant <i>Enterococcus</i> spp. |
| title_full | Antimicrobial Activity of Ceragenins against Vancomycin-Susceptible and -Resistant <i>Enterococcus</i> spp. |
| title_fullStr | Antimicrobial Activity of Ceragenins against Vancomycin-Susceptible and -Resistant <i>Enterococcus</i> spp. |
| title_full_unstemmed | Antimicrobial Activity of Ceragenins against Vancomycin-Susceptible and -Resistant <i>Enterococcus</i> spp. |
| title_short | Antimicrobial Activity of Ceragenins against Vancomycin-Susceptible and -Resistant <i>Enterococcus</i> spp. |
| title_sort | antimicrobial activity of ceragenins against vancomycin susceptible and resistant i enterococcus i spp |
| topic | <i>Enterococcus</i> spp. ceragenin linezolid minimum inhibitory concentration microbroth checkerboard <i>Caenorhabditis elegans</i> |
| url | https://www.mdpi.com/1424-8247/16/12/1643 |
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