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. 2023 Nov 23;16(12):1643.
doi: 10.3390/ph16121643.

Antimicrobial Activity of Ceragenins against Vancomycin-Susceptible and -Resistant Enterococcus spp

Mayram Hacioglu  1 , Fatima Nur Yilmaz  1 , Ozlem Oyardi  2 , Cagla Bozkurt Guzel  1 , Nese Inan  3 , Paul B Savage  4 , Sibel Dosler  1
Affiliations

Antimicrobial Activity of Ceragenins against Vancomycin-Susceptible and -Resistant Enterococcus spp

Mayram Hacioglu et al. Pharmaceuticals (Basel). .

Abstract

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 Enterococcus spp. (17 of them vancomycin-resistant Enterococcus-VRE) isolated from various clinical specimens. Among the ceragenins evaluated, the MIC50 and MIC90 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 Enterococcus 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 Caenorhabditis elegans model system. Compared to no treatment, increased survival was observed with C. elegans 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.

Keywords: Caenorhabditis elegans; Enterococcus spp.; ceragenin; linezolid; microbroth checkerboard; minimum inhibitory concentration.

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Conflict of interest statement

Author P.B.S. was a consultant for the company N8 Medical, Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Bactericidal activity of CSA-192 and linezolid (MIC) against three Enterococcus spp. strains by using the time-kill curve method. (a) VRE strain; (b,c) vancomycin-susceptible strain L: Linezolid.
Figure 2
Figure 2
(a) Percent survival of infected C. elegans (average ± SD) after treatment with CSA-44 and CSA-192 at concentrations of 2 and 4 µg/mL. The results were expressed as the percent survival after 24, 48, and 72 h of infection, respectively. (b) Cytotoxicity of ceragenins; nematode survival rates. Compounds were tested twice in each assay. Each assay was replicated at least three times. Statistical analysis for both figures were performed with GraphPad Prism 8. The data were not statistically significant when compared to the control group.
Figure 3
Figure 3
Chemical structures of studied CSAs.
See this image and copyright information in PMC

References

    1. Agudelo Higuita N.I., Huycke M.M. Enterococcal Disease, Epidemiology, and Implications for Treatment. In: Gilmore M.S., Clewell D.B., Ike Y., Shankar N., editors. Enterococci: From Commensals to Leading Causes of Drug Resistant Infection. Massachusetts Eye and Ear Infirmary; Boston, MA, USA: 2014. pp. 65–100. - PubMed
    1. Garcia-Solache M., Rice L.B. The Enterococcus: A model of adaptability to its environment. Clin. Microbiol. Rev. 2019;32:e00058-18. doi: 10.1128/CMR.00058-18. - DOI - PMC - PubMed
    1. Selleck E.M., Van Tyne D., Gilmore M.S. Pathogenicity of enterococci. Microbiol. Spectr. 2019;7 doi: 10.1128/microbiolspec.GPP3-0053-2018. - DOI - PMC - PubMed
    1. Codelia-Anjum A., Lerner L.B., Elterman D., Zorn K.C., Bhojani N., Chughtai B. Enterococcal Urinary Tract Infections: A Review of the Pathogenicity, Epidemiology, and Treatment. Antibiotics. 2023;12:778. doi: 10.3390/antibiotics12040778. - DOI - PMC - PubMed
    1. Miller W.R., Murray B.E., Rice L.B., Arias C.A. Resistance in Vancomycin-Resistant Enterococci. Infect. Dis. Clin. N. Am. 2020;34:751–771. doi: 10.1016/j.idc.2020.08.004. - DOI - PMC - PubMed

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