Ceragenin CSA-13 displays high antibacterial efficiency in a mouse model of urinary tract infection.
Urszula Wnorowska, Ewelina Piktel, Piotr Deptuła, Tomasz Wollny, Grzegorz Król, Katarzyna Głuszek, Bonita Durnaś, Katarzyna Pogoda, Paul B Savage, Robert Bucki
Author Information
Urszula Wnorowska: Department of Medical Microbiology and Nanobiomedical Engineering, Medical University of Białystok, Mickiewicza 2C, 15-222, Białystok, Poland.
Ewelina Piktel: Independent Laboratory of Nanomedicine, Medical University of Białystok, Mickiewicza 2B, 15-222, Białystok, Poland.
Piotr Deptuła: Independent Laboratory of Nanomedicine, Medical University of Białystok, Mickiewicza 2B, 15-222, Białystok, Poland.
Tomasz Wollny: Holy Cross Oncology Center of Kielce, Artwińskiego 3, 25-734, Kielce, Poland.
Grzegorz Król: Institute of Medical Science, Collegium Medicum, Jan Kochanowski University of Kielce, IX Wieków Kielc 19A, 25-317, Kielce, Poland.
Katarzyna Głuszek: Institute of Medical Science, Collegium Medicum, Jan Kochanowski University of Kielce, 25-001, Kielce, Poland.
Bonita Durnaś: Institute of Medical Science, Collegium Medicum, Jan Kochanowski University of Kielce, IX Wieków Kielc 19A, 25-317, Kielce, Poland.
Katarzyna Pogoda: Institute of Nuclear Physics Polish Academy of Sciences, 31-342, Kraków, Poland. ORCID
Paul B Savage: Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, 84602, USA.
Robert Bucki: Department of Medical Microbiology and Nanobiomedical Engineering, Medical University of Białystok, Mickiewicza 2C, 15-222, Białystok, Poland. buckirobert@gmail.com. ORCID
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.
