title: Bactericidal Activity of Ceragenin CSA-13 in Cell Culture and in an Animal Model of Peritoneal Infection.
abstract: Ceragenins constitute a novel family of cationic antibiotics characterized by a broad spectrum of antimicrobial activities, which have mostly been assessed in vitro. Using a polarized human lung epithelial cell culture system, we evaluated the antibacterial activities of the ceragenin CSA-13 against two strains of Pseudomonas aeruginosa (PAO1 and Xen5). Additionally, the biodistribution and bactericidal activity of a CSA-13-IRDye 800CW derivate were assessed using an animal model of peritoneal infection after PAO1 challenge. In cell culture, CSA-13 bactericidal activities against PAO1 and Xen5 were higher than the activities of the human cathelicidin peptide LL-37. Increased CSA-13 activity was observed in polarized human lung epithelial cell cultures subjected to butyric acid treatment, which is known to increase endogenous LL-37 production. Eight hours after intravenous or intraperitoneal injection, the greatest CSA-13-IRDye 800CW accumulation was observed in mouse liver and kidneys. CSA-13-IRDye 800CW administration resulted in decreased bacterial outgrowth from abdominal fluid collected from animals subjected to intraperitoneal PAO1 infection. These observations indicate that CSA-13 may synergistically interact with antibacterial factors that are naturally present at mucosal surfaces and it maintains its antibacterial activity in the infected abdominal cavity. Cationic lipids such as CSA-13 represent excellent candidates for the development of new antibacterial compounds.
authors.affiliation: Department of Microbiological and Nanobiomedical Engineering, Medical University of Bialystok, Bialystok, Poland Department of Physiology, Pathophysiology, and Microbiology of Infections, Faculty of Health Sciences, Jan Kochanowski University in Kielce, Kielce, Poland University of Pennsylvania, Institute for Medicine and Engineering, Roy and Diana Vagelos Research Laboratories, Philadelphia, Pennsylvania, USA buckirobert@gmail.com.
authors.forename: Robert
authors.initials: R
authors.lastname: Bucki
authors.affiliation: Department of Microbiological and Nanobiomedical Engineering, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Niemirowicz
authors.affiliation: Department of Microbiological and Nanobiomedical Engineering, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Urszula
authors.initials: U
authors.lastname: Wnorowska
authors.affiliation: University of Pennsylvania, Institute for Medicine and Engineering, Roy and Diana Vagelos Research Laboratories, Philadelphia, Pennsylvania, USA.
authors.forename: Fitzroy J
authors.initials: FJ
authors.lastname: Byfield
authors.affiliation: Department of Microbiological and Nanobiomedical Engineering, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Ewelina
authors.initials: E
authors.lastname: Piktel
authors.affiliation: Department of Hematology, Holy Cross Oncology Center, Kielce, Poland.
authors.forename: Marzena
authors.initials: M
authors.lastname: Wątek
authors.affiliation: University of Pennsylvania, Institute for Medicine and Engineering, Roy and Diana Vagelos Research Laboratories, Philadelphia, Pennsylvania, USA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Janmey
authors.affiliation: Department of Chemistry and Biochemistry, Brigham Young University, Provo, Utah, USA.
authors.forename: Paul B
authors.initials: PB
authors.lastname: Savage
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000493:pharmacokinetics / Q000494:pharmacology; D001682:Biological Availability; D020148:Butyric Acid / Q000494:pharmacology; D002460:Cell Line; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D005260:Female; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D008826:Microbial Sensitivity Tests; D010538:Peritonitis / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000254:growth & development; D020545:Respiratory Mucosa / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D013256:Steroids / Q000493:pharmacokinetics / Q000494:pharmacology*; D054804:Cathelicidins
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D005456:Fluorescent Dyes; D013256:Steroids; C521528:ceragenin CSA-13; D020148:Butyric Acid; D054804:Cathelicidins