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Ceragenin CSA-13 displays high antibacterial efficiency in a mouse model of urinary tract infection
Ceragenins (CSAs) are synthetic, lipid-based molecules that display activities of natural antimicrobial peptides. Previous studies demonstrated their high in vitro activity against pathogens causing urinary tract infections (UTIs), but their efficiency in vivo was not explored to date. In this study...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9649698/ https://www.ncbi.nlm.nih.gov/pubmed/36357517 http://dx.doi.org/10.1038/s41598-022-23281-y |
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author | Wnorowska, Urszula Piktel, Ewelina Deptuła, Piotr Wollny, Tomasz Król, Grzegorz Głuszek, Katarzyna Durnaś, Bonita Pogoda, Katarzyna Savage, Paul B. Bucki, Robert |
author_facet | Wnorowska, Urszula Piktel, Ewelina Deptuła, Piotr Wollny, Tomasz Król, Grzegorz Głuszek, Katarzyna Durnaś, Bonita Pogoda, Katarzyna Savage, Paul B. Bucki, Robert |
author_sort | Wnorowska, Urszula |
collection | PubMed |
description | Ceragenins (CSAs) are synthetic, lipid-based molecules that display activities of natural antimicrobial peptides. Previous studies demonstrated their high in vitro activity against pathogens causing urinary tract infections (UTIs), but their efficiency in vivo was not explored to date. In this study, we aimed to investigate the bactericidal efficiency of ceragenins against E. coli (Xen14 and clinical UPEC strains) isolates both in vitro and in vivo, as well to explore CSA-13 biodistribution and ability to modulate nanomechanical alterations of infected tissues using animal model of UTI. CSA-44, CSA-131 and particularly CSA-13 displayed potent bactericidal effect against tested E. coli strains, and this effect was mediated by induction of oxidative stress. Biodistribution studies indicated that CSA-13 accumulates in kidneys and liver and is eliminated with urine and bile acid. We also observed that ceragenin CSA-13 reverses infection-induced alterations in mechanical properties of mouse bladders tissue, which confirms the preventive role of CSA-13 against bacteria-induced tissue damage and potentially promote the restoration of microenvironment with biophysical features unfavorable for bacterial growth and spreading. These data justify the further work on employment of CSA-13 in the treatment of urinary tract infections. |
format | Online Article Text |
id | pubmed-9649698 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-96496982022-11-15 Ceragenin CSA-13 displays high antibacterial efficiency in a mouse model of urinary tract infection Wnorowska, Urszula Piktel, Ewelina Deptuła, Piotr Wollny, Tomasz Król, Grzegorz Głuszek, Katarzyna Durnaś, Bonita Pogoda, Katarzyna Savage, Paul B. Bucki, Robert Sci Rep Article Ceragenins (CSAs) are synthetic, lipid-based molecules that display activities of natural antimicrobial peptides. Previous studies demonstrated their high in vitro activity against pathogens causing urinary tract infections (UTIs), but their efficiency in vivo was not explored to date. In this study, we aimed to investigate the bactericidal efficiency of ceragenins against E. coli (Xen14 and clinical UPEC strains) isolates both in vitro and in vivo, as well to explore CSA-13 biodistribution and ability to modulate nanomechanical alterations of infected tissues using animal model of UTI. CSA-44, CSA-131 and particularly CSA-13 displayed potent bactericidal effect against tested E. coli strains, and this effect was mediated by induction of oxidative stress. Biodistribution studies indicated that CSA-13 accumulates in kidneys and liver and is eliminated with urine and bile acid. We also observed that ceragenin CSA-13 reverses infection-induced alterations in mechanical properties of mouse bladders tissue, which confirms the preventive role of CSA-13 against bacteria-induced tissue damage and potentially promote the restoration of microenvironment with biophysical features unfavorable for bacterial growth and spreading. These data justify the further work on employment of CSA-13 in the treatment of urinary tract infections. Nature Publishing Group UK 2022-11-10 /pmc/articles/PMC9649698/ /pubmed/36357517 http://dx.doi.org/10.1038/s41598-022-23281-y Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Wnorowska, Urszula Piktel, Ewelina Deptuła, Piotr Wollny, Tomasz Król, Grzegorz Głuszek, Katarzyna Durnaś, Bonita Pogoda, Katarzyna Savage, Paul B. Bucki, Robert Ceragenin CSA-13 displays high antibacterial efficiency in a mouse model of urinary tract infection |
title | Ceragenin CSA-13 displays high antibacterial efficiency in a mouse model of urinary tract infection |
title_full | Ceragenin CSA-13 displays high antibacterial efficiency in a mouse model of urinary tract infection |
title_fullStr | Ceragenin CSA-13 displays high antibacterial efficiency in a mouse model of urinary tract infection |
title_full_unstemmed | Ceragenin CSA-13 displays high antibacterial efficiency in a mouse model of urinary tract infection |
title_short | Ceragenin CSA-13 displays high antibacterial efficiency in a mouse model of urinary tract infection |
title_sort | ceragenin csa-13 displays high antibacterial efficiency in a mouse model of urinary tract infection |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9649698/ https://www.ncbi.nlm.nih.gov/pubmed/36357517 http://dx.doi.org/10.1038/s41598-022-23281-y |
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