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: Robert Bucki, Katarzyna Niemirowicz, Urszula Wnorowska, Fitzroy J Byfield, Ewelina Piktel, Marzena Wątek, Paul A Janmey, Paul B Savage
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 59 Issue 10 Pg. 6274-82 (Oct 2015) ISSN: 1098-6596 [Electronic] United States
• PMID: 26248361 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Chemical References

• Anti-Bacterial Agents
• Antimicrobial Cationic Peptides
• Fluorescent Dyes
• Steroids
• ceragenin CSA-13
• Butyric Acid
• Cathelicidins

Topics

• Animals
• Anti-Bacterial Agents (pharmacokinetics, pharmacology)
• Antimicrobial Cationic Peptides (pharmacokinetics, pharmacology)
• Biological Availability
• Butyric Acid (pharmacology)
• Cell Line
• Disease Models, Animal
• Epithelial Cells (drug effects, microbiology, pathology)
• Female
• Fluorescent Dyes (chemistry)
• Humans
• Injections, Intraperitoneal
• Kidney (drug effects, metabolism)
• Liver (drug effects, metabolism)
• Lung (drug effects, microbiology, pathology)
• Mice
• Mice, Nude
• Microbial Sensitivity Tests
• Peritonitis (drug therapy, microbiology, pathology)
• Pseudomonas Infections (drug therapy, microbiology, pathology)
• Pseudomonas aeruginosa (drug effects, growth & development)
• Respiratory Mucosa (drug effects, microbiology, pathology)
• Steroids (pharmacokinetics, pharmacology)
• Cathelicidins